NM_001098484.3:c.808-11971C>A

Variant names:

• chr4-71428645-C-A
• rs4626166
• NM_001098484.3:c.808-11971C>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.808-11971C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,156 control chromosomes in the GnomAD database, including 3,296 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 0.20 (3296 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• 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: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.41 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	NM_001098484.3	MANE Select	c.808-11971C>A		intron	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_003759.4	MANE Plus Clinical	c.676-11971C>A		intron	N/A	NP_003750.1	Q9Y6R1-2
	SLC4A4	NM_001440629.1		c.901-11971C>A		intron	N/A	NP_001427558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.808-11971C>A		intron	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000340595.4	TSL:1 MANE Plus Clinical	c.676-11971C>A		intron	N/A	ENSP00000344272.3	Q9Y6R1-2
	SLC4A4	ENST00000351898.10	TSL:1	c.808-11971C>A		intron	N/A	ENSP00000307349.7	Q9Y6R1-4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29907 AN: 151040 Hom.: 3285 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.198 AC: 29956 AN: 151156 Hom.: 3296 Cov.: 32 AF XY: 0.203 AC XY: 14963 AN XY: 73816

African (AFR) AF: 0.197 AC: 8110 AN: 41158

American (AMR) AF: 0.320 AC: 4849 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3462

East Asian (EAS) AF: 0.206 AC: 1052 AN: 5110

South Asian (SAS) AF: 0.426 AC: 2046 AN: 4808

European-Finnish (FIN) AF: 0.124 AC: 1286 AN: 10396

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11326 AN: 67772

Other (OTH) AF: 0.190 AC: 400 AN: 2102

Alfa AF: 0.0978 Hom.: 152

Bravo AF: 0.206

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		0.32
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: rs4626166; hg19: chr4-72294362;