7-151070453-C-T

Variant names:

• chr7-151070453-C-T
• rs2303934
• NM_003040.4:c.1450-4C>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.1450-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 1,611,352 control chromosomes in the GnomAD database, including 1,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (134 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1457 hom.)
• Consequence: SLC4A2 NM_003040.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008835
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 12 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0887 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.1450-4C>T		splice_region intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.1450-4C>T		splice_region intron	N/A	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.1423-4C>T		splice_region 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.1450-4C>T		splice_region intron	N/A	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.1450-4C>T		splice_region intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.1408-4C>T		splice_region intron	N/A	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4778 AN: 152186 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.00787

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0272

GnomAD2 exomes AF: 0.0449 AC: 10966 AN: 244164 AF XY: 0.0480

Gnomad AFR exome AF: 0.00721

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.0250

Gnomad NFE exome AF: 0.0378

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0391 AC: 57111 AN: 1459048 Hom.: 1457 Cov.: 33 AF XY: 0.0409 AC XY: 29666 AN XY: 725766

African (AFR) AF: 0.00724 AC: 242 AN: 33414

American (AMR) AF: 0.0183 AC: 813 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3167 AN: 26048

East Asian (EAS) AF: 0.0994 AC: 3927 AN: 39514

South Asian (SAS) AF: 0.0712 AC: 6122 AN: 86042

European-Finnish (FIN) AF: 0.0263 AC: 1388 AN: 52724

Middle Eastern (MID) AF: 0.0838 AC: 482 AN: 5750

European-Non Finnish (NFE) AF: 0.0343 AC: 38144 AN: 1110908

Other (OTH) AF: 0.0469 AC: 2826 AN: 60270

GnomAD4 genome AF: 0.0314 AC: 4780 AN: 152304 Hom.: 134 Cov.: 33 AF XY: 0.0324 AC XY: 2410 AN XY: 74474

African (AFR) AF: 0.00784 AC: 326 AN: 41556

American (AMR) AF: 0.0227 AC: 348 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5172

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4834

European-Finnish (FIN) AF: 0.0208 AC: 221 AN: 10626

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2389 AN: 68018

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0369 Hom.: 286

Bravo AF: 0.0303

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.1
DANN	Benign	0.83
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000088
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.11		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: rs2303934; hg19: chr7-150767540; COSMIC: COSV59656028; COSMIC: COSV59656028;