rs9997927

Positions:

• chr4-71492383-C-A
• chr4-71492383-C-T

Variant summary

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

The NM_001098484.3(SLC4A4):​c.1975-5118C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,606 control chromosomes in the GnomAD database, including 26,292 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 0.56 (26292 hom., cov: 31)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.1975-5118C>A		intron_variant		ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.1843-5118C>A		intron_variant		ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1975-5118C>A		intron_variant		1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.1843-5118C>A		intron_variant		1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84623 AN: 151486 Hom.: 26289 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.558 AC: 84650 AN: 151606 Hom.: 26292 Cov.: 31 AF XY: 0.553 AC XY: 40938 AN XY: 74056

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.565

Alfa AF: 0.606 Hom.: 7641

Bravo AF: 0.531

Asia WGS AF: 0.378 AC: 1310 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.19

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: rs9997927; hg19: chr4-72358100;