4-126627517-A-T

Variant names:

• chr4-126627517-A-T
• rs432446
• ENST00000661809.1:n.148+70748T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000661809.1(ENSG00000286251):​n.148+70748T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,876 control chromosomes in the GnomAD database, including 2,425 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 0.17 (2425 hom., cov: 31)
• Consequence: ENSG00000286251 ENST00000661809.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

Genes affected

ENSG00000286251 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286251	ENST00000661809.1	n.148+70748T>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26009 AN: 151758 Hom.: 2419 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00580

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.171 AC: 26040 AN: 151876 Hom.: 2425 Cov.: 31 AF XY: 0.168 AC XY: 12503 AN XY: 74242

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.00562

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.146

Alfa AF: 0.197 Hom.: 346

Bravo AF: 0.162

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs432446; hg19: chr4-127548672;