chr4-71123704-T-C

Position:

• chr4-71123704-T-C

Variant summary

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

The ENST00000649996.1(SLC4A4):​c.-2+30912T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,168 control chromosomes in the GnomAD database, including 2,328 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 0.16 (2328 hom., cov: 32)
• Consequence: SLC4A4 ENST00000649996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	XM_024454268.2	c.14+30912T>C		intron_variant			XP_024310036.1
SLC4A4	XM_024454269.2	c.14+30912T>C		intron_variant			XP_024310037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000649996.1	c.-2+30912T>C		intron_variant				ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-2+30912T>C		intron_variant				ENSP00000513771.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25051 AN: 152050 Hom.: 2318 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.165 AC: 25087 AN: 152168 Hom.: 2328 Cov.: 32 AF XY: 0.164 AC XY: 12212 AN XY: 74386

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.157

Alfa AF: 0.149 Hom.: 1462

Bravo AF: 0.168

Asia WGS AF: 0.252 AC: 871 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16845804; hg19: chr4-71989421;