rs4973768

Variant names:

• chr3-27374522-C-T
• rs4973768
• NM_001321103.2:c.*2242G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321103.2(SLC4A7):​c.*2242G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,260 control chromosomes in the GnomAD database, including 15,155 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 0.44 (15123 hom., cov: 33)
  • Exomes 𝑓: 0.40 (32 hom.)
• Consequence: SLC4A7 NM_001321103.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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]

ENSG00000287348 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.*2242G>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389	c.*2242G>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_001321103.2	ENSP00000390394.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66738 AN: 151730 Hom.: 15122 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.402 AC: 165 AN: 410 Hom.: 32 Cov.: 0 AF XY: 0.360 AC XY: 90 AN XY: 250

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.401 AC: 162 AN: 404

Gnomad4 NFE exome AF: 1.00 AC: 2 AN: 2

Gnomad4 Remaining exome AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.440 AC: 66758 AN: 151850 Hom.: 15123 Cov.: 33 AF XY: 0.440 AC XY: 32658 AN XY: 74202

Gnomad4 AFR AF: 0.358 AC: 0.357694 AN: 0.357694

Gnomad4 AMR AF: 0.537 AC: 0.536823 AN: 0.536823

Gnomad4 ASJ AF: 0.563 AC: 0.562572 AN: 0.562572

Gnomad4 EAS AF: 0.192 AC: 0.191995 AN: 0.191995

Gnomad4 SAS AF: 0.441 AC: 0.440994 AN: 0.440994

Gnomad4 FIN AF: 0.447 AC: 0.447069 AN: 0.447069

Gnomad4 NFE AF: 0.477 AC: 0.476545 AN: 0.476545

Gnomad4 OTH AF: 0.471 AC: 0.471063 AN: 0.471063

Alfa AF: 0.467 Hom.: 78340

Bravo AF: 0.444

Asia WGS AF: 0.368 AC: 1276 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.85
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

Publications

LitVar

Other links and lift over

dbSNP: rs4973768; hg19: chr3-27416013; COSMIC: COSV55394698; COSMIC: COSV55394698;