rs73394838

chr22-29829984-A-G

Variant summary

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

The NM_032204.5(ASCC2):c.81+2261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,140 control chromosomes in the GnomAD database, including 2,136 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 0.13 (2136 hom., cov: 32)
• Consequence: ASCC2 NM_032204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

Genes affected

ASCC2 (HGNC:24103): (activating signal cointegrator 1 complex subunit 2) Predicted to enable ubiquitin binding activity. Involved in regulation of transcription, DNA-templated; rescue of stalled ribosome; and ribosome-associated ubiquitin-dependent protein catabolic process. Located in nucleus. Part of activating signal cointegrator 1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCC2	NM_032204.5	c.81+2261T>C		intron_variant		ENST00000307790.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASCC2	ENST00000307790.8	c.81+2261T>C		intron_variant		1	NM_032204.5	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19984 AN: 152022 Hom.: 2136 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20011 AN: 152140 Hom.: 2136 Cov.: 32 AF XY: 0.132 AC XY: 9807 AN XY: 74414

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0619

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0879 Hom.: 194

Bravo AF: 0.143

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.23
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs73394838; hg19: chr22-30225973;