chr4-71123704-T-C

Variant names:

• chr4-71123704-T-C
• rs16845804
• NM_001440628.1:c.14+30912T>C

Variant summary

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

The NM_001440628.1(SLC4A4):​c.14+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 NM_001440628.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 4 publications found

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]

SLC4A4 Gene-Disease associations (from GenCC):

• autosomal recessive proximal renal tubular acidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC4A4	NM_001440628.1	c.14+30912T>C		intron_variant	Intron 2 of 26		NP_001427557.1
SLC4A4	XM_024454268.2	c.14+30912T>C		intron_variant	Intron 3 of 27		XP_024310036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000649996.1	c.-2+30912T>C		intron_variant	Intron 2 of 26			ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-2+30912T>C		intron_variant	Intron 3 of 26			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

African (AFR) AF: 0.235 AC: 9760 AN: 41504

American (AMR) AF: 0.103 AC: 1577 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4818

European-Finnish (FIN) AF: 0.100 AC: 1063 AN: 10596

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9173 AN: 68010

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.150 Hom.: 1716

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
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs16845804; hg19: chr4-71989421;