rs7685921

Variant names:

• chr4-71162828-A-G
• rs7685921
• NM_001440628.1:c.14+70036A>G

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+70036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,136 control chromosomes in the GnomAD database, including 2,843 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 0.18 (2843 hom., cov: 32)
• Consequence: SLC4A4 NM_001440628.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001440628.1	c.14+70036A>G		intron_variant	Intron 2 of 26		NP_001427557.1
SLC4A4	XM_024454268.2	c.14+70036A>G		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+70036A>G		intron_variant	Intron 2 of 26			ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-2+70036A>G		intron_variant	Intron 3 of 26			ENSP00000513771.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26874 AN: 152018 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.177 AC: 26908 AN: 152136 Hom.: 2843 Cov.: 32 AF XY: 0.180 AC XY: 13404 AN XY: 74374

African (AFR) AF: 0.231 AC: 9580 AN: 41468

American (AMR) AF: 0.280 AC: 4278 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3468

East Asian (EAS) AF: 0.119 AC: 616 AN: 5184

South Asian (SAS) AF: 0.345 AC: 1662 AN: 4816

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10610

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8583 AN: 68008

Other (OTH) AF: 0.169 AC: 356 AN: 2108

Alfa AF: 0.159 Hom.: 351

Bravo AF: 0.188

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.57
PhyloP100		0.88

Splicing

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

Other links and lift over

dbSNP: rs7685921; hg19: chr4-72028545;