chr3-27375508-T-C

Position:

• chr3-27375508-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454389.6(SLC4A7):​c.*1256A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,114 control chromosomes in the GnomAD database, including 15,355 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 (15319 hom., cov: 32)
  • Exomes 𝑓: 0.40 (36 hom.)
• Consequence: SLC4A7 ENST00000454389.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.*1256A>G		3_prime_UTR_variant	26/26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.*1256A>G		3_prime_UTR_variant	26/26	1	NM_001321103.2	ENSP00000390394
	ENST00000661166.1	n.975+4966T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67099 AN: 151570 Hom.: 15318 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.404 AC: 173 AN: 428 Hom.: 36 Cov.: 0 AF XY: 0.364 AC XY: 94 AN XY: 258

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.442 AC: 67118 AN: 151686 Hom.: 15319 Cov.: 32 AF XY: 0.443 AC XY: 32817 AN XY: 74150

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.474

Alfa AF: 0.480 Hom.: 3084

Bravo AF: 0.447

Asia WGS AF: 0.368 AC: 1270 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.7
DANN	Benign	0.66

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: rs1051545; hg19: chr3-27416999;