chr3-27433860-G-A

Position:

• chr3-27433860-G-A

Variant summary

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

The NM_001321103.2(SLC4A7):​c.778+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,413,372 control chromosomes in the GnomAD database, including 10,596 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 0.13 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9381 hom.)
• Consequence: SLC4A7 NM_001321103.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A7	NM_001321103.2	c.778+56C>T		intron_variant		ENST00000454389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A7	ENST00000454389.6	c.778+56C>T		intron_variant		1	NM_001321103.2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19252 AN: 152030 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.118 AC: 148218 AN: 1261222 Hom.: 9381 AF XY: 0.116 AC XY: 73700 AN XY: 638018

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0952

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0626

Gnomad4 SAS exome AF: 0.0423

Gnomad4 FIN exome AF: 0.0985

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.127 AC: 19249 AN: 152150 Hom.: 1215 Cov.: 32 AF XY: 0.124 AC XY: 9248 AN XY: 74356

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0537

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.135

Alfa AF: 0.135 Hom.: 2076

Bravo AF: 0.130

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.60
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3278; hg19: chr3-27475351; COSMIC: COSV55402522;