NM_001321103.2:c.3516T>C

Variant names:

• chr3-27383227-A-G
• rs1472256
• NM_001321103.2:c.3516T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001321103.2(SLC4A7):​c.3516T>C​(p.Asp1172Asp) 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 NM_001321103.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 20 publications found

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]

SLC4A7 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• cone-rod dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ENSG00000287348 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321103.2. 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
	SLC4A7	NM_001321103.2	MANE Select	c.3516T>C	p.Asp1172Asp	synonymous	Exon 24 of 26	NP_001308032.1	Q9Y6M7-7
	SLC4A7	NM_001321104.2		c.3477T>C	p.Asp1159Asp	synonymous	Exon 24 of 26	NP_001308033.1	Q9Y6M7-8
	SLC4A7	NM_003615.5		c.3489T>C	p.Asp1163Asp	synonymous	Exon 24 of 25	NP_003606.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	ENST00000454389.6	TSL:1 MANE Select	c.3516T>C	p.Asp1172Asp	synonymous	Exon 24 of 26	ENSP00000390394.1	Q9Y6M7-7
	SLC4A7	ENST00000440156.5	TSL:1	c.3477T>C	p.Asp1159Asp	synonymous	Exon 24 of 26	ENSP00000414797.1	Q9Y6M7-8
	SLC4A7	ENST00000295736.9	TSL:1	c.3489T>C	p.Asp1163Asp	synonymous	Exon 24 of 25	ENSP00000295736.5	Q9Y6M7-1

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

GnomAD2 exomes AF: 0.941 AC: 235740 AN: 250614 AF XY: 0.939

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 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

African (AFR) AF: 0.871 AC: 29125 AN: 33422

American (AMR) AF: 0.974 AC: 43437 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 24326 AN: 26102

East Asian (EAS) AF: 1.00 AC: 39671 AN: 39676

South Asian (SAS) AF: 0.924 AC: 79396 AN: 85956

European-Finnish (FIN) AF: 0.925 AC: 49384 AN: 53392

Middle Eastern (MID) AF: 0.908 AC: 5230 AN: 5758

European-Non Finnish (NFE) AF: 0.940 AC: 1043686 AN: 1110174

Other (OTH) AF: 0.940 AC: 56686 AN: 60322

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

African (AFR) AF: 0.878 AC: 36448 AN: 41530

American (AMR) AF: 0.952 AC: 14561 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3248 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 0.938 AC: 4521 AN: 4818

European-Finnish (FIN) AF: 0.928 AC: 9839 AN: 10600

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.941 AC: 63978 AN: 68022

Other (OTH) AF: 0.928 AC: 1961 AN: 2114

Alfa AF: 0.936 Hom.: 132048

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1472256; hg19: chr3-27424718; COSMIC: COSV108089825; COSMIC: COSV108089825;