3-27383227-A-G

Position:

• chr3-27383227-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000454389.6(SLC4A7):​c.3516T>C​(p.Asp1172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,611,614 control chromosomes in the GnomAD database, including 709,600 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 0.93 (65255 hom., cov: 32)
  • Exomes 𝑓: 0.94 (644345 hom.)
• Consequence: SLC4A7 ENST00000454389.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

Genes affected

SLC4A7 (HGNC:11033): (solute carrier family 4 member 7) This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.621 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.3516T>C	p.Asp1172=	synonymous_variant	24/26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.3516T>C	p.Asp1172=	synonymous_variant	24/26	1	NM_001321103.2	ENSP00000390394
	ENST00000661166.1	n.976-4445A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140709 AN: 152120 Hom.: 65203 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.926

GnomAD3 exomes AF: 0.941 AC: 235740 AN: 250614 Hom.: 111024 AF XY: 0.939 AC XY: 127181 AN XY: 135416

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.977

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.924

Gnomad FIN exome AF: 0.925

Gnomad NFE exome AF: 0.938

Gnomad OTH exome AF: 0.939

GnomAD4 exome AF: 0.939 AC: 1370941 AN: 1459376 Hom.: 644345 Cov.: 37 AF XY: 0.939 AC XY: 681787 AN XY: 726108

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.974

Gnomad4 ASJ exome AF: 0.932

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.924

Gnomad4 FIN exome AF: 0.925

Gnomad4 NFE exome AF: 0.940

Gnomad4 OTH exome AF: 0.940

GnomAD4 genome AF: 0.925 AC: 140821 AN: 152238 Hom.: 65255 Cov.: 32 AF XY: 0.926 AC XY: 68936 AN XY: 74424

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.928

Alfa AF: 0.937 Hom.: 108424

Bravo AF: 0.924

Asia WGS AF: 0.968 AC: 3367 AN: 3478

EpiCase AF: 0.940

EpiControl AF: 0.943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs1472256; hg19: chr3-27424718;