10-45015960-A-G

Position:

• chr10-45015960-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000456938.6(ENSG00000293022):​n.618+2T>C variant causes a splice donor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,158 control chromosomes in the GnomAD database, including 39,995 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 0.72 (39994 hom., cov: 33)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: ENST00000456938.6 splice_donor, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75

Genes affected

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.754 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
	ENST00000456938.6	n.618+2T>C		splice_donor_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110097 AN: 152034 Hom.: 39965 Cov.: 33

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.724 AC: 110179 AN: 152152 Hom.: 39994 Cov.: 33 AF XY: 0.726 AC XY: 53990 AN XY: 74360

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.723

Alfa AF: 0.717 Hom.: 52060

Bravo AF: 0.728

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.027
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6593456; hg19: chr10-45511408;