7-151068149-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

SLC4A2 Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 4

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• osteopetrosis, autosomal recessive 9

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	NM_003040.4	MANE Select	c.1147+95G>A		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.1147+95G>A		intron	N/A	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.1120+95G>A		intron	N/A	NP_001186622.1	Q59GF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.1147+95G>A		intron	N/A	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.1147+95G>A		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.1105+95G>A		intron	N/A	ENSP00000419164.1	P04920-2

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

African (AFR) AF: 0.0817 AC: 1361 AN: 16660

American (AMR) AF: 0.109 AC: 1091 AN: 9980

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 2413 AN: 14950

East Asian (EAS) AF: 0.0235 AC: 620 AN: 26436

South Asian (SAS) AF: 0.266 AC: 10809 AN: 40560

European-Finnish (FIN) AF: 0.144 AC: 4473 AN: 30990

Middle Eastern (MID) AF: 0.190 AC: 565 AN: 2968

European-Non Finnish (NFE) AF: 0.207 AC: 130459 AN: 629334

Other (OTH) AF: 0.184 AC: 6853 AN: 37258

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

African (AFR) AF: 0.0886 AC: 3681 AN: 41550

American (AMR) AF: 0.126 AC: 1923 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3464

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5186

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10566

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13989 AN: 68000

Other (OTH) AF: 0.160 AC: 339 AN: 2116

Alfa AF: 0.173 Hom.: 3178

Bravo AF: 0.145

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.68
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12703112; hg19: chr7-150765236;