rs11766855

Variant names:

• chr7-151075830-C-T
• rs11766855
• NM_003040.4:c.3471+55C>T

Variant summary

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

The NM_003040.4(SLC4A2):​c.3471+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,556,726 control chromosomes in the GnomAD database, including 26,524 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 (1803 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24721 hom.)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 6 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

ENSG00000244151 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 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.3471+55C>T		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.3471+55C>T		intron	N/A	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.3444+55C>T		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.3471+55C>T		intron	N/A	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.3471+55C>T		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.3429+55C>T		intron	N/A	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22256 AN: 152022 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.181 AC: 254811 AN: 1404584 Hom.: 24721 Cov.: 28 AF XY: 0.184 AC XY: 127432 AN XY: 693044

African (AFR) AF: 0.0925 AC: 2971 AN: 32134

American (AMR) AF: 0.0923 AC: 3744 AN: 40572

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3658 AN: 23450

East Asian (EAS) AF: 0.0155 AC: 603 AN: 39022

South Asian (SAS) AF: 0.271 AC: 21762 AN: 80392

European-Finnish (FIN) AF: 0.134 AC: 6764 AN: 50364

Middle Eastern (MID) AF: 0.192 AC: 937 AN: 4890

European-Non Finnish (NFE) AF: 0.190 AC: 204169 AN: 1075954

Other (OTH) AF: 0.177 AC: 10203 AN: 57806

GnomAD4 genome AF: 0.146 AC: 22261 AN: 152142 Hom.: 1803 Cov.: 32 AF XY: 0.143 AC XY: 10627 AN XY: 74380

African (AFR) AF: 0.102 AC: 4246 AN: 41506

American (AMR) AF: 0.124 AC: 1891 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3468

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5182

South Asian (SAS) AF: 0.269 AC: 1291 AN: 4806

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10610

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12469 AN: 67958

Other (OTH) AF: 0.147 AC: 310 AN: 2116

Alfa AF: 0.149 Hom.: 1384

Bravo AF: 0.139

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.033
DANN	Benign	0.64
PhyloP100		-1.9
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: rs11766855; hg19: chr7-150772917; COSMIC: COSV52540085; COSMIC: COSV52540085;