rs145031776

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173076.3(ABCA12):c.6648G>T(p.Arg2216Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,613,134 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 144 hom. )

Consequence

ABCA12
NM_173076.3 missense, splice_region

Scores

Splicing: ADA: 0.7538

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00100

Publications

6 publications found

Variant links:

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ABCA12 links:

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

SNHG31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002706021).

BP6

Variant 2-214951083-C-A is Benign according to our data. Variant chr2-214951083-C-A is described in ClinVar as Benign. ClinVar VariationId is 262832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173076.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA12	NM_173076.3	MANE Select	c.6648G>T	p.Arg2216Ser	missense splice_region	Exon 45 of 53	NP_775099.2
ABCA12	NM_015657.4		c.5694G>T	p.Arg1898Ser	missense splice_region	Exon 37 of 45	NP_056472.2
ABCA12	NR_103740.2		n.7146G>T		splice_region non_coding_transcript_exon	Exon 47 of 55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.6648G>T	p.Arg2216Ser	missense splice_region	Exon 45 of 53	ENSP00000272895.7	Q86UK0-1
ABCA12	ENST00000389661.4	TSL:1	c.5694G>T	p.Arg1898Ser	missense splice_region	Exon 37 of 45	ENSP00000374312.4	Q86UK0-2
SNHG31	ENST00000607412.2	TSL:2	n.473+3136C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.0121

AC:

3026

AN:

250774

AF XY:

0.00934

show subpopulations

Gnomad AFR exome

AF:

0.00192

Gnomad AMR exome

AF:

0.0815

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.00917

GnomAD4 exome

AF:

0.00279

AC:

4082

AN:

1460900

Hom.:

144

Cov.:

AF XY:

0.00247

AC XY:

1794

AN XY:

726800

show subpopulations

African (AFR)

AF:

0.000927

AC:

AN:

33458

American (AMR)

AF:

0.0760

AC:

3397

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.00183

AC:

158

AN:

86230

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

53172

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000295

AC:

328

AN:

1111370

Other (OTH)

AF:

0.00257

AC:

155

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

221

442

662

883

1104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00591

AC:

900

AN:

152234

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

504

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41560

American (AMR)

AF:

0.0512

AC:

783

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68004

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00965

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00919

AC:

1116

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital ichthyosis of skin (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.081

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.8

PhyloP100

0.0010

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.64

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

0.42

Vest4

0.63

MutPred

0.47

Loss of MoRF binding (P = 0.0293)

MPC

0.67

ClinPred

0.040

GERP RS

2.0

Varity_R

0.36

gMVP

0.78

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.75

dbscSNV1_RF

Benign

0.72

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.34

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over