NM_003040.4:c.320G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003040.4(SLC4A2):c.320G>A(p.Arg107Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,613,592 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 7 hom. )

Consequence

SLC4A2
NM_003040.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.82

Publications

4 publications found

Variant links:

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

SLC4A2 Gene-Disease associations (from GenCC):

hereditary spherocytosis type 4
Inheritance: AD Classification: MODERATE Submitted by: G2P
osteopetrosis, autosomal recessive 9
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SLC4A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009216309).

BP6

Variant 7-151064628-G-A is Benign according to our data. Variant chr7-151064628-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658176.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A2	NM_003040.4	MANE Select	c.320G>A	p.Arg107Gln	missense	Exon 4 of 23	NP_003031.3
SLC4A2	NM_001199692.3		c.320G>A	p.Arg107Gln	missense	Exon 4 of 23	NP_001186621.1	P04920-1
SLC4A2	NM_001199693.1		c.293G>A	p.Arg98Gln	missense	Exon 3 of 22	NP_001186622.1	Q59GF1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.320G>A	p.Arg107Gln	missense	Exon 4 of 23	ENSP00000405600.2	P04920-1
SLC4A2	ENST00000485713.6	TSL:1	c.320G>A	p.Arg107Gln	missense	Exon 4 of 23	ENSP00000419412.1
SLC4A2	ENST00000461735.1	TSL:1	c.278G>A	p.Arg93Gln	missense	Exon 3 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

302

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00145

AC:

360

AN:

247496

AF XY:

0.00150

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00270

AC:

3952

AN:

1461328

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

1944

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.000598

AC:

AN:

33464

American (AMR)

AF:

0.000403

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000487

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.000506

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00327

AC:

3641

AN:

1111832

Other (OTH)

AF:

0.00320

AC:

193

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

232

464

695

927

1159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00199

AC:

303

AN:

152264

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41544

American (AMR)

AF:

0.00131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68004

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00258

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00157

AC:

190

EpiCase

AF:

0.00360

EpiControl

AF:

0.00160

ClinVar

ClinVar submissions

Significance:Likely 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

0.098

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.057

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.4

PhyloP100

2.8

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

REVEL

Benign

0.075

Sift

Benign

0.052

Sift4G

Pathogenic

0.0

Polyphen

0.028

Vest4

0.20

MVP

0.66

MPC

0.66

ClinPred

0.016

GERP RS

4.4

Varity_R

0.059

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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