7-151066295-C-T

Variant names:

• chr7-151066295-C-T
• rs35576067
• NM_003040.4:c.579-222C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. 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
	SLC4A2	NM_003040.4	MANE Select	c.579-222C>T		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.579-222C>T		intron	N/A	NP_001186621.1
	SLC4A2	NM_001199693.1		c.552-222C>T		intron	N/A	NP_001186622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.579-222C>T		intron	N/A	ENSP00000405600.2
	SLC4A2	ENST00000485713.6	TSL:1	c.579-222C>T		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.537-222C>T		intron	N/A	ENSP00000419164.1

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

African (AFR) AF: 0.00464 AC: 193 AN: 41590

American (AMR) AF: 0.00999 AC: 153 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4832

European-Finnish (FIN) AF: 0.0747 AC: 793 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2172 AN: 68028

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0281 Hom.: 118

Bravo AF: 0.0173

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.87
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35576067; hg19: chr7-150763382;