7-151064771-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003040.4(SLC4A2):c.459+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,607,068 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: SLC4A2 NM_003040.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0009315
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.751

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 7-151064771-C-T is Benign according to our data. Variant chr7-151064771-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.459+4C>T		splice_donor_region_variant, intron_variant		ENST00000413384.7
SLC4A2	NM_001199692.3	c.459+4C>T		splice_donor_region_variant, intron_variant
SLC4A2	NM_001199693.1	c.432+4C>T		splice_donor_region_variant, intron_variant
SLC4A2	NM_001199694.2	c.417+4C>T		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.459+4C>T		splice_donor_region_variant, intron_variant		1	NM_003040.4	P1

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152184 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000896 AC: 221 AN: 246738 Hom.: 3 AF XY: 0.000778 AC XY: 104 AN XY: 133682

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.0158

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000994

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000441

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.000563 AC: 819 AN: 1454766 Hom.: 6 Cov.: 36 AF XY: 0.000561 AC XY: 405 AN XY: 722486

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000315

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152302 Hom.: 1 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74474

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00179 Hom.: 2

Bravo AF: 0.000729

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

SLC4A2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	11
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00093
dbscSNV1_RF	Benign	0.098
SpliceAI score (max)		0.10		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: rs35021531; hg19: chr7-150761858;