rs4663105

Variant names:

• chr2-127133851-A-C
• rs4663105
• ENST00000726607.1:n.342-1409A>C

Variant summary

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

The ENST00000726607.1(ENSG00000294899):​n.342-1409A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,642 control chromosomes in the GnomAD database, including 16,715 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 0.46 (16715 hom., cov: 30)
• Consequence: ENSG00000294899 ENST00000726607.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 52 publications found

Genes affected

ENSG00000294899 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373605	XR_923310.3	n.513+549A>C		intron_variant	Intron 3 of 3
LOC105373605	XR_923311.4	n.910+549A>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294899	ENST00000726607.1	n.342-1409A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70057 AN: 151522 Hom.: 16652 Cov.: 30

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70188 AN: 151642 Hom.: 16715 Cov.: 30 AF XY: 0.462 AC XY: 34258 AN XY: 74108

African (AFR) AF: 0.572 AC: 23641 AN: 41326

American (AMR) AF: 0.464 AC: 7070 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2334 AN: 5128

South Asian (SAS) AF: 0.475 AC: 2278 AN: 4800

European-Finnish (FIN) AF: 0.399 AC: 4174 AN: 10470

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27929 AN: 67888

Other (OTH) AF: 0.425 AC: 895 AN: 2104

Alfa AF: 0.443 Hom.: 1906

Bravo AF: 0.470

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.28
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4663105; hg19: chr2-127891427;