NM_003040.4:c.1147+95G>A

Variant names:

• chr7-151068149-G-A
• rs12703112
• NM_003040.4:c.1147+95G>A

Variant summary

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

The NM_003040.4(SLC4A2):​c.1147+95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 961,352 control chromosomes in the GnomAD database, including 19,075 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 0.15 (2078 hom., cov: 33)
  • Exomes 𝑓: 0.20 (16997 hom.)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.1147+95G>A		intron_variant	Intron 8 of 22	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.1147+95G>A		intron_variant	Intron 8 of 22		NP_001186621.1
SLC4A2	NM_001199693.1	c.1120+95G>A		intron_variant	Intron 7 of 21		NP_001186622.1
SLC4A2	NM_001199694.2	c.1105+95G>A		intron_variant	Intron 7 of 21		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.1147+95G>A		intron_variant	Intron 8 of 22	1	NM_003040.4	ENSP00000405600.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23419 AN: 152098 Hom.: 2078 Cov.: 33

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.196 AC: 158644 AN: 809136 Hom.: 16997 AF XY: 0.198 AC XY: 79303 AN XY: 399806

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.0235

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.154 AC: 23430 AN: 152216 Hom.: 2078 Cov.: 33 AF XY: 0.150 AC XY: 11143 AN XY: 74400

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.160

Alfa AF: 0.179 Hom.: 2184

Bravo AF: 0.145

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12703112; hg19: chr7-150765236;