rs7571842

Positions:

• chr2-74233777-A-G
• chr2-74233777-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133478.3(SLC4A5):​c.2434-214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,014 control chromosomes in the GnomAD database, including 22,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (22337 hom., cov: 32)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.623

Genes affected

SLC4A5 (HGNC:18168): (solute carrier family 4 member 5) This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-74233777-A-G is Benign according to our data. Variant chr2-74233777-A-G is described in ClinVar as [Benign]. Clinvar id is 1235516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2434-214T>C		intron_variant		ENST00000394019.7	NP_597812.1
SLC4A5	NM_001386136.1	c.2086-214T>C		intron_variant			NP_001373065.1
SLC4A5	NM_021196.3	c.2434-214T>C		intron_variant			NP_067019.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2434-214T>C		intron_variant		5	NM_133478.3	ENSP00000377587	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81017 AN: 151892 Hom.: 22308 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.533 AC: 81096 AN: 152014 Hom.: 22337 Cov.: 32 AF XY: 0.536 AC XY: 39854 AN XY: 74312

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.525

Alfa AF: 0.467 Hom.: 9622

Bravo AF: 0.546

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 29642240) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.80

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: rs7571842; hg19: chr2-74460904;