rs6854303

Variant names:

• chr4-71417036-G-A
• rs6854303
• NM_001098484.3:c.807+19383G>A

Variant summary

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

The NM_001098484.3(SLC4A4):​c.807+19383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,980 control chromosomes in the GnomAD database, including 30,954 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 0.61 (30954 hom., cov: 31)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• 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 (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098484.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	NM_001098484.3	MANE Select	c.807+19383G>A		intron	N/A	NP_001091954.1
	SLC4A4	NM_003759.4	MANE Plus Clinical	c.675+19383G>A		intron	N/A	NP_003750.1
	SLC4A4	NM_001440629.1		c.900+19383G>A		intron	N/A	NP_001427558.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.807+19383G>A		intron	N/A	ENSP00000264485.5
	SLC4A4	ENST00000340595.4	TSL:1 MANE Plus Clinical	c.675+19383G>A		intron	N/A	ENSP00000344272.3
	SLC4A4	ENST00000351898.10	TSL:1	c.807+19383G>A		intron	N/A	ENSP00000307349.7

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92776 AN: 151862 Hom.: 30954 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.611 AC: 92799 AN: 151980 Hom.: 30954 Cov.: 31 AF XY: 0.608 AC XY: 45133 AN XY: 74280

African (AFR) AF: 0.356 AC: 14745 AN: 41414

American (AMR) AF: 0.563 AC: 8601 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2405 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3251 AN: 5132

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4818

European-Finnish (FIN) AF: 0.815 AC: 8616 AN: 10576

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51193 AN: 67984

Other (OTH) AF: 0.638 AC: 1346 AN: 2110

Alfa AF: 0.705 Hom.: 163983

Bravo AF: 0.589

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.83
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6854303; hg19: chr4-72282753;