chr4-99144358-T-G

Position:

• chr4-99144358-T-G

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-10187T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 832,468 control chromosomes in the GnomAD database, including 155,044 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 0.50 (21619 hom., cov: 31)
  • Exomes 𝑓: 0.62 (133425 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-10187T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.680-10187T>G		intron_variant		1
ADH4	ENST00000504581.1	n.170-1578A>C		intron_variant		3
ENSG00000246090	ENST00000661393.1	n.676+10553T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75940 AN: 151898 Hom.: 21616 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.615 AC: 418577 AN: 680452 Hom.: 133425 AF XY: 0.625 AC XY: 225031 AN XY: 359780

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.799

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.598

GnomAD4 genome AF: 0.500 AC: 75962 AN: 152016 Hom.: 21619 Cov.: 31 AF XY: 0.507 AC XY: 37686 AN XY: 74296

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.519

Alfa AF: 0.580 Hom.: 34895

Bravo AF: 0.471

Asia WGS AF: 0.744 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800759; hg19: chr4-100065509; COSMIC: COSV55501258;