Genetic Variant SLC4A2:c.218-65A>G (chr7-151064461-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003040.4(SLC4A2):c.218-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,563,010 control chromosomes in the GnomAD database, including 98,054 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 0.34 ( 8459 hom., cov: 25)

Exomes 𝑓: 0.35 ( 89595 hom. )

Consequence

SLC4A2
NM_003040.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.47

Publications

7 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 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

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	Effect	Exon Rank	Protein
SLC4A2	NM_003040.4	MANE Select	c.218-65A>G	intron	N/A	NP_003031.3
SLC4A2	NM_001199692.3		c.218-65A>G	intron	N/A	NP_001186621.1
SLC4A2	NM_001199693.1		c.191-65A>G	intron	N/A	NP_001186622.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.218-65A>G	intron	N/A	ENSP00000405600.2
SLC4A2	ENST00000485713.6	TSL:1	c.218-65A>G	intron	N/A	ENSP00000419412.1
SLC4A2	ENST00000461735.1	TSL:1	c.176-65A>G	intron	N/A	ENSP00000419164.1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

49076

AN:

145220

Hom.:

8454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.374

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.353

AC:

500682

AN:

1417694

Hom.:

89595

Cov.:

AF XY:

0.352

AC XY:

246462

AN XY:

699732

show subpopulations

African (AFR)

AF:

0.260

AC:

8500

AN:

32748

American (AMR)

AF:

0.218

AC:

9342

AN:

42824

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

10094

AN:

23790

East Asian (EAS)

AF:

0.323

AC:

12650

AN:

39168

South Asian (SAS)

AF:

0.298

AC:

24206

AN:

81334

European-Finnish (FIN)

AF:

0.423

AC:

21757

AN:

51454

Middle Eastern (MID)

AF:

0.369

AC:

1468

AN:

3980

European-Non Finnish (NFE)

AF:

0.361

AC:

391767

AN:

1084072

Other (OTH)

AF:

0.358

AC:

20898

AN:

58324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15938

31876

47814

63752

79690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12536

25072

37608

50144

62680

<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:

0.338

AC:

49111

AN:

145316

Hom.:

8459

Cov.:

AF XY:

0.339

AC XY:

23954

AN XY:

70716

show subpopulations

African (AFR)

AF:

0.271

AC:

10452

AN:

38574

American (AMR)

AF:

0.317

AC:

4626

AN:

14604

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1392

AN:

3374

East Asian (EAS)

AF:

0.321

AC:

1564

AN:

4868

South Asian (SAS)

AF:

0.287

AC:

1318

AN:

4588

European-Finnish (FIN)

AF:

0.434

AC:

4261

AN:

9820

Middle Eastern (MID)

AF:

0.378

AC:

109

AN:

288

European-Non Finnish (NFE)

AF:

0.368

AC:

24421

AN:

66296

Other (OTH)

AF:

0.352

AC:

713

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1387

2774

4162

5549

6936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.343

Hom.:

1112

Bravo

AF:

0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

(source)

DANN

Benign

0.37

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(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