7-151061731-C-G

Variant names:

• chr7-151061731-C-G
• rs13240966
• NM_003040.4:c.-63-194C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003040.4(SLC4A2):​c.-63-194C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 489,892 control chromosomes in the GnomAD database, including 8,292 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 0.16 (2204 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6088 hom.)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43
• Publications: 3 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

LOC128092247 (HGNC:0):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 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.-63-194C>G		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.-63-194C>G		intron	N/A	NP_001186621.1	P04920-1
	LOC128092247	NM_001414898.1	MANE Select	c.-197C>G		upstream_gene	N/A	NP_001401827.1	A0A6Q8PFQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.-63-194C>G		intron	N/A	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.-63-194C>G		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000488420.1	TSL:3	c.-257C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000417221.1	C9J459

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24252 AN: 152088 Hom.: 2204 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.174 AC: 58922 AN: 337686 Hom.: 6088 Cov.: 0 AF XY: 0.179 AC XY: 31347 AN XY: 175136

African (AFR) AF: 0.101 AC: 1126 AN: 11114

American (AMR) AF: 0.107 AC: 1637 AN: 15334

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 1699 AN: 11132

East Asian (EAS) AF: 0.0153 AC: 434 AN: 28298

South Asian (SAS) AF: 0.243 AC: 5653 AN: 23266

European-Finnish (FIN) AF: 0.140 AC: 3207 AN: 22938

Middle Eastern (MID) AF: 0.170 AC: 274 AN: 1608

European-Non Finnish (NFE) AF: 0.203 AC: 41402 AN: 203636

Other (OTH) AF: 0.171 AC: 3490 AN: 20360

GnomAD4 genome AF: 0.159 AC: 24275 AN: 152206 Hom.: 2204 Cov.: 32 AF XY: 0.155 AC XY: 11519 AN XY: 74408

African (AFR) AF: 0.106 AC: 4396 AN: 41546

American (AMR) AF: 0.127 AC: 1947 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.0161 AC: 83 AN: 5146

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10616

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14117 AN: 67986

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.0649 Hom.: 80

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.057
DANN	Benign	0.42
PhyloP100		-3.4
PromoterAI		-0.072	Neutral
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: rs13240966; hg19: chr7-150758818;