rs35576067

Positions:

• chr7-151066295-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003040.4(SLC4A2):​c.579-222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,342 control chromosomes in the GnomAD database, including 64 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 0.023 (64 hom., cov: 34)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3488/152342) while in subpopulation NFE AF= 0.0319 (2172/68028). AF 95% confidence interval is 0.0308. There are 64 homozygotes in gnomad4. There are 1818 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.579-222C>T		intron_variant		ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.579-222C>T		intron_variant			NP_001186621.1
SLC4A2	NM_001199693.1	c.552-222C>T		intron_variant			NP_001186622.1
SLC4A2	NM_001199694.2	c.537-222C>T		intron_variant			NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.579-222C>T		intron_variant		1	NM_003040.4	ENSP00000405600	P1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3488 AN: 152224 Hom.: 64 Cov.: 34

Gnomad AFR AF: 0.00465

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0186

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

GnomAD4 genome AF: 0.0229 AC: 3488 AN: 152342 Hom.: 64 Cov.: 34 AF XY: 0.0244 AC XY: 1818 AN XY: 74492

Gnomad4 AFR AF: 0.00464

Gnomad4 AMR AF: 0.00999

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0304 Hom.: 10

Bravo AF: 0.0173

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35576067; hg19: chr7-150763382;