rs545021444

Variant names:

• chr4-71339279-A-C
• NM_003759.4:c.31A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-71339279-A-C
• chr4-71339279-A-G
• chr4-71339279-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003759.4(SLC4A4):​c.31A>C​(p.Ser11Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC4A4 NM_003759.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12462795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_003759.4	c.31A>C	p.Ser11Arg	missense_variant	Exon 1 of 23	ENST00000340595.4	NP_003750.1
SLC4A4	NM_001098484.3	c.254-91A>C		intron_variant	Intron 3 of 25	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000340595.4	c.31A>C	p.Ser11Arg	missense_variant	Exon 1 of 23	1	NM_003759.4	ENSP00000344272.3
SLC4A4	ENST00000264485.11	c.254-91A>C		intron_variant	Intron 3 of 25	1	NM_001098484.3	ENSP00000264485.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.084
Eigen_PC	Benign	0.034
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.51	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.32	T;T
Polyphen		0.023	B;B
Vest4		0.14
MutPred		0.17		Gain of MoRF binding (P = 0.0137);Gain of MoRF binding (P = 0.0137);
MVP		0.068
ClinPred		0.44	T
GERP RS		4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-72204996;