chr4-71564850-A-T

Variant names:

• chr4-71564850-A-T
• rs1453456
• NM_001098484.3:c.3196+961A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098484.3(SLC4A4):​c.3196+961A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.3196+961A>T		intron	N/A	NP_001091954.1
	SLC4A4	NM_003759.4	MANE Plus Clinical	c.3064+961A>T		intron	N/A	NP_003750.1
	SLC4A4	NM_001440629.1		c.3289+961A>T		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.3196+961A>T		intron	N/A	ENSP00000264485.5
	SLC4A4	ENST00000340595.4	TSL:1 MANE Plus Clinical	c.3064+961A>T		intron	N/A	ENSP00000344272.3
	SLC4A4	ENST00000351898.10	TSL:1	c.2944+961A>T		intron	N/A	ENSP00000307349.7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151754 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151754 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74102

African (AFR) AF: 0.00 AC: 0 AN: 41320

American (AMR) AF: 0.00 AC: 0 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67886

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.40
PhyloP100		-0.065

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: rs1453456; hg19: chr4-72430567;