rs33966546

chr7-151062891-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000461735.1(SLC4A2):c.-290C>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 0.262 in 1,389,776 control chromosomes in the GnomAD database, including 49,090 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 0.27 (5917 hom., cov: 32)
  • Exomes 𝑓: 0.26 (43173 hom.)
• Consequence: SLC4A2 ENST00000461735.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.51+853C>T		intron_variant		ENST00000413384.7
SLC4A2	NM_001199694.2	c.-290C>T		5_prime_UTR_variant	1/22
SLC4A2	NM_001199692.3	c.51+853C>T		intron_variant
SLC4A2	NM_001199693.1	c.24+228C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.51+853C>T		intron_variant		1	NM_003040.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41140 AN: 151848 Hom.: 5904 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.261 AC: 323117 AN: 1237810 Hom.: 43173 Cov.: 36 AF XY: 0.259 AC XY: 155030 AN XY: 598026

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.271 AC: 41163 AN: 151966 Hom.: 5917 Cov.: 32 AF XY: 0.272 AC XY: 20194 AN XY: 74278

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.270

Alfa AF: 0.280 Hom.: 776

Bravo AF: 0.286

Asia WGS AF: 0.209 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.9
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs33966546; hg19: chr7-150759978;