rs371330147

Variant names:

• chr7-151064312-C-T
• rs371330147
• NM_003040.4:c.162C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151064312-C-T
• chr7-151064312-C-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003040.4(SLC4A2):​c.162C>T​(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000685 in 1,415,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000069 (1 hom.)
• Consequence: SLC4A2 NM_003040.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.92
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 7-151064312-C-T is Benign according to our data. Variant chr7-151064312-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.92 with no splicing effect.

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.162C>T	p.Ala54Ala	synonymous	Exon 3 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.162C>T	p.Ala54Ala	synonymous	Exon 3 of 23	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.135C>T	p.Ala45Ala	synonymous	Exon 2 of 22	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.162C>T	p.Ala54Ala	synonymous	Exon 3 of 23	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.162C>T	p.Ala54Ala	synonymous	Exon 3 of 23	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.120C>T	p.Ala40Ala	synonymous	Exon 2 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes AF: 0.0000606 AC: 8 AN: 132110 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000800

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000792

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000721 AC: 18 AN: 249654 AF XY: 0.0000813

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000694 AC: 89 AN: 1283272 Hom.: 1 Cov.: 36 AF XY: 0.0000723 AC XY: 46 AN XY: 636004

African (AFR) AF: 0.00 AC: 0 AN: 28596

American (AMR) AF: 0.00 AC: 0 AN: 39438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19698

East Asian (EAS) AF: 0.00 AC: 0 AN: 23450

South Asian (SAS) AF: 0.000520 AC: 44 AN: 84592

European-Finnish (FIN) AF: 0.0000266 AC: 1 AN: 37618

Middle Eastern (MID) AF: 0.000280 AC: 1 AN: 3566

European-Non Finnish (NFE) AF: 0.0000341 AC: 34 AN: 997600

Other (OTH) AF: 0.000185 AC: 9 AN: 48714

GnomAD4 genome AF: 0.0000605 AC: 8 AN: 132188 Hom.: 0 Cov.: 29 AF XY: 0.0000635 AC XY: 4 AN XY: 63002

African (AFR) AF: 0.00 AC: 0 AN: 35892

American (AMR) AF: 0.00 AC: 0 AN: 12034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3250

East Asian (EAS) AF: 0.00 AC: 0 AN: 4006

South Asian (SAS) AF: 0.000800 AC: 3 AN: 3752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000792 AC: 5 AN: 63168

Other (OTH) AF: 0.00 AC: 0 AN: 1870

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000416

EpiCase AF: 0.000110

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.2
DANN	Benign	0.88
PhyloP100		-5.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs371330147; hg19: chr7-150761399; COSMIC: COSV59657739; COSMIC: COSV59657739;