12-49588455-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032130.3(FAM186B):c.2533C>T(p.Arg845Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,610,608 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

FAM186B
NM_032130.3 missense, splice_region

Scores

Splicing: ADA: 0.001258

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.333

Publications

5 publications found

Variant links:

Genes affected

FAM186B (HGNC:25296): (family with sequence similarity 186 member B) This gene product is a member of the FAM186 family, however, its exact function is not known. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

FAM186B links:

PRPF40B (HGNC:25031): (pre-mRNA processing factor 40 homolog B) This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants. [provided by RefSeq, Aug 2014]

PRPF40B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029908419).

BP6

Variant 12-49588455-G-A is Benign according to our data. Variant chr12-49588455-G-A is described in ClinVar as Benign. ClinVar VariationId is 1601350.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00119 (181/152318) while in subpopulation EAS AF = 0.0295 (153/5194). AF 95% confidence interval is 0.0257. There are 4 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032130.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186B	NM_032130.3	MANE Select	c.2533C>T	p.Arg845Cys	missense splice_region	Exon 6 of 7	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2875C>T		splice_region non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2533C>T	p.Arg845Cys	missense splice_region	Exon 6 of 7	ENSP00000257894.2	Q8IYM0-1
FAM186B	ENST00000532262.5	TSL:1	c.1372C>T	p.Arg458Cys	missense splice_region	Exon 3 of 5	ENSP00000436995.1	A0A0C4DGG0
FAM186B	ENST00000548841.5	TSL:5	c.202C>T	p.Arg68Cys	missense splice_region	Exon 2 of 4	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0294

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00242

AC:

602

AN:

248840

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00107

AC:

1562

AN:

1458290

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

726

AN XY:

724942

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33434

American (AMR)

AF:

0.0000675

AC:

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.0334

AC:

1322

AN:

39570

South Asian (SAS)

AF:

0.000268

AC:

AN:

85890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1109792

Other (OTH)

AF:

0.00287

AC:

173

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00119

AC:

181

AN:

152318

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41570

American (AMR)

AF:

0.000262

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0295

AC:

153

AN:

5194

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

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:

0.00134

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00226

AC:

274

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.95

PhyloP100

-0.33

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.069

Sift

Benign

0.069

Sift4G

Uncertain

0.039

Polyphen

0.010

Vest4

0.18

MVP

0.048

MPC

0.18

ClinPred

0.019

GERP RS

-1.5

Varity_R

0.052

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.16

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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