rs10446758

chr4-148526433-T-Cchr4-148526433-T-G

Variant summary

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

The ENST00000661928.1(ENSG00000287292):n.105-18034T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 606,578 control chromosomes in the GnomAD database, including 77,805 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 0.44 (16130 hom., cov: 29)
  • Exomes 𝑓: 0.51 (61675 hom.)
• Consequence: ENST00000661928.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000661928.1	n.105-18034T>C		intron_variant, non_coding_transcript_variant
	ENST00000669991.1	n.169-18031T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66622 AN: 151474 Hom.: 16116 Cov.: 29

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.508 AC: 230964 AN: 454984 Hom.: 61675 AF XY: 0.506 AC XY: 129232 AN XY: 255456

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.672

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.440 AC: 66666 AN: 151594 Hom.: 16130 Cov.: 29 AF XY: 0.455 AC XY: 33670 AN XY: 74032

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.434

Alfa AF: 0.388 Hom.: 1774

Bravo AF: 0.432

Asia WGS AF: 0.687 AC: 2385 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.9
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10446758; hg19: chr4-149447585;