4-74556244-A-G

Position:

• chr4-74556244-A-G

Variant summary

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

The ENST00000510419.1(ENSG00000249942):​n.374-144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,066 control chromosomes in the GnomAD database, including 29,084 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 0.60 (29084 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000249942 ENST00000510419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

Genes affected

ENSG00000249942 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107986229	XR_001741513.2	n.174-3412T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000249942	ENST00000510419.1	n.374-144T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91235 AN: 151948 Hom.: 29070 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.581

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.600 AC: 91281 AN: 152066 Hom.: 29084 Cov.: 32 AF XY: 0.613 AC XY: 45562 AN XY: 74342

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.586

Alfa AF: 0.622 Hom.: 3898

Bravo AF: 0.587

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9996584; hg19: chr4-75421961;