dbSNP rs2069441: SLC4A2:c.-1034C>T (chr7-151058218-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001199692.3(SLC4A2):c.-1034C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 365,556 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 50 hom., cov: 33)

Exomes 𝑓: 0.022 ( 71 hom. )

Consequence

SLC4A2
NM_001199692.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0186 (2826/152334) while in subpopulation NFE AF = 0.0267 (1813/68026). AF 95% confidence interval is 0.0256. There are 50 homozygotes in GnomAd4. There are 1387 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199692.3. 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
	SLC4A2	NM_001199692.3		c.-1034C>T		5_prime_UTR	Exon 1 of 23	NP_001186621.1	P04920-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A2	ENST00000485713.6	TSL:1	c.-1034C>T	5_prime_UTR	Exon 1 of 23	ENSP00000419412.1
SLC4A2	ENST00000483786.5	TSL:4	c.-64+937C>T	intron	N/A	ENSP00000417808.1	C9J722
SLC4A2	ENST00000466368.1	TSL:4	n.19C>T	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2826

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0165

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0389

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0186

GnomAD4 exome

AF:

0.0222

AC:

4740

AN:

213222

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

2368

AN XY:

111346

show subpopulations

African (AFR)

AF:

0.00487

AC:

AN:

4928

American (AMR)

AF:

0.0132

AC:

AN:

7404

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

110

AN:

6740

East Asian (EAS)

AF:

0.0000772

AC:

AN:

12956

South Asian (SAS)

AF:

0.00637

AC:

131

AN:

20574

European-Finnish (FIN)

AF:

0.0413

AC:

607

AN:

14710

Middle Eastern (MID)

AF:

0.0199

AC:

AN:

956

European-Non Finnish (NFE)

AF:

0.0263

AC:

3473

AN:

132012

Other (OTH)

AF:

0.0214

AC:

277

AN:

12942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

217

435

652

870

1087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0186

AC:

2826

AN:

152334

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1387

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00493

AC:

205

AN:

41572

American (AMR)

AF:

0.0165

AC:

253

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0389

AC:

413

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0267

AC:

1813

AN:

68026

Other (OTH)

AF:

0.0184

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

143

286

430

573

716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0213

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

(source)

DANN

Benign

0.78

PhyloP100

-0.24

PromoterAI

-0.049

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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