4-174524086-A-G

Position:

• chr4-174524086-A-G

Variant summary

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

The ENST00000515178.1(ENSG00000250596):​n.1817T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,150 control chromosomes in the GnomAD database, including 17,691 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 0.47 (17683 hom., cov: 32)
  • Exomes 𝑓: 0.54 (8 hom.)
• Consequence: ENSG00000250596 ENST00000515178.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

ENSG00000250596 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377548	XR_007058493.1	n.628A>G		non_coding_transcript_exon_variant	1/6
LOC105377548	XR_007058487.1	n.809+665A>G		intron_variant
LOC105377548	XR_007058488.1	n.318+1156A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000250596	ENST00000515178.1	n.1817T>C		non_coding_transcript_exon_variant	3/3	1
ENSG00000251584	ENST00000664316.1	n.314+1156A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71156 AN: 151986 Hom.: 17681 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.543 AC: 25 AN: 46 Hom.: 8 Cov.: 0 AF XY: 0.528 AC XY: 19 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.468 AC: 71181 AN: 152104 Hom.: 17683 Cov.: 32 AF XY: 0.466 AC XY: 34656 AN XY: 74338

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.500

Alfa AF: 0.520 Hom.: 9591

Bravo AF: 0.462

Asia WGS AF: 0.490 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756273; hg19: chr4-175445237;