7-151070453-C-T

Variant summary

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

The NM_003040.4(SLC4A2):c.1450-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 1,611,352 control chromosomes in the GnomAD database, including 1,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (134 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1457 hom.)
• Consequence: SLC4A2 NM_003040.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008835
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.1450-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000413384.7
SLC4A2	NM_001199692.3	c.1450-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC4A2	NM_001199693.1	c.1423-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC4A2	NM_001199694.2	c.1408-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.1450-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003040.4	P1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4778 AN: 152186 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.00787

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.0449 AC: 10966 AN: 244164 Hom.: 381 AF XY: 0.0480 AC XY: 6358 AN XY: 132576

Gnomad AFR exome AF: 0.00721

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.0714

Gnomad FIN exome AF: 0.0250

Gnomad NFE exome AF: 0.0378

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0391 AC: 57111 AN: 1459048 Hom.: 1457 Cov.: 33 AF XY: 0.0409 AC XY: 29666 AN XY: 725766

Gnomad4 AFR exome AF: 0.00724

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0994

Gnomad4 SAS exome AF: 0.0712

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0343

Gnomad4 OTH exome AF: 0.0469

GnomAD4 genome AF: 0.0314 AC: 4780 AN: 152304 Hom.: 134 Cov.: 33 AF XY: 0.0324 AC XY: 2410 AN XY: 74474

Gnomad4 AFR AF: 0.00784

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.0679

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0324 Hom.: 74

Bravo AF: 0.0303

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	9.1
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000088
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.11		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: rs2303934; hg19: chr7-150767540; COSMIC: COSV59656028; COSMIC: COSV59656028;