rs2069441

chr7-151058218-C-T

Variant summary

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

The ENST00000485713.5(SLC4A2):c.-1034C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 365,556 control chromosomes in the GnomAD database, including 121 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 0.019 (50 hom., cov: 33)
  • Exomes 𝑓: 0.022 (71 hom.)
• Consequence: SLC4A2 ENST00000485713.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2826/152334) while in subpopulation NFE AF= 0.0267 (1813/68026). AF 95% confidence interval is 0.0256. There are 50 homozygotes in gnomad4. There are 1387 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_001199692.3	c.-1034C>T		5_prime_UTR_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000485713.5	c.-1034C>T		5_prime_UTR_variant	1/23	1		P1
SLC4A2	ENST00000483786.5	c.-64+937C>T		intron_variant		4
SLC4A2	ENST00000466368.1	n.19C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2826 AN: 152216 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.0222 AC: 4740 AN: 213222 Hom.: 71 Cov.: 0 AF XY: 0.0213 AC XY: 2368 AN XY: 111346

Gnomad4 AFR exome AF: 0.00487

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0000772

Gnomad4 SAS exome AF: 0.00637

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0186 AC: 2826 AN: 152334 Hom.: 50 Cov.: 33 AF XY: 0.0186 AC XY: 1387 AN XY: 74486

Gnomad4 AFR AF: 0.00493

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0213 Hom.: 6

Bravo AF: 0.0171

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.8
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2069441; hg19: chr7-150755305;