4-99144442-T-C

Position:

• chr4-99144442-T-C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-10103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 422,244 control chromosomes in the GnomAD database, including 126,498 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 0.77 (45546 hom., cov: 32)
  • Exomes 𝑓: 0.76 (80952 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-10103T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.680-10103T>C		intron_variant		1
ADH4	ENST00000504581.1	n.170-1662A>G		intron_variant		3
ENSG00000246090	ENST00000661393.1	n.676+10637T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116470 AN: 152018 Hom.: 45515 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.756 AC: 204143 AN: 270108 Hom.: 80952 AF XY: 0.756 AC XY: 105400 AN XY: 139448

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.766

GnomAD4 genome AF: 0.766 AC: 116549 AN: 152136 Hom.: 45546 Cov.: 32 AF XY: 0.763 AC XY: 56707 AN XY: 74368

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.780

Alfa AF: 0.791 Hom.: 5936

Bravo AF: 0.763

Asia WGS AF: 0.590 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.98
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800761; hg19: chr4-100065593;