4-71217657-C-T

Variant names:

• chr4-71217657-C-T
• rs7689609
• NM_001098484.3:c.-1-18919C>T

Variant summary

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

The NM_001134742.2(SLC4A4):​c.-1-18919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,174 control chromosomes in the GnomAD database, including 37,214 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 0.63 (37214 hom., cov: 33)
• Consequence: SLC4A4 NM_001134742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 11 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134742.2. 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.-1-18919C>T		intron	N/A	NP_001091954.1
	SLC4A4	NM_001134742.2		c.-1-18919C>T		intron	N/A	NP_001128214.1
	SLC4A4	NM_001440628.1		c.15-18919C>T		intron	N/A	NP_001427557.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.-1-18919C>T		intron	N/A	ENSP00000264485.5
	SLC4A4	ENST00000351898.10	TSL:1	c.-1-18919C>T		intron	N/A	ENSP00000307349.7
	SLC4A4	ENST00000895605.1		c.-1-18919C>T		intron	N/A	ENSP00000565664.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95616 AN: 152056 Hom.: 37212 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.628 AC: 95619 AN: 152174 Hom.: 37214 Cov.: 33 AF XY: 0.628 AC XY: 46743 AN XY: 74408

African (AFR) AF: 0.158 AC: 6557 AN: 41474

American (AMR) AF: 0.691 AC: 10557 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2705 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2717 AN: 5172

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4820

European-Finnish (FIN) AF: 0.893 AC: 9476 AN: 10612

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58620 AN: 68020

Other (OTH) AF: 0.658 AC: 1393 AN: 2116

Alfa AF: 0.770 Hom.: 76558

Bravo AF: 0.596

Asia WGS AF: 0.481 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.7
DANN	Benign	0.79
PhyloP100		0.55
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: rs7689609; hg19: chr4-72083374;