rs73394838

Variant names:

• chr22-29829984-A-G
• rs73394838
• NM_032204.5:c.81+2261T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASCC2	NM_032204.5	c.81+2261T>C		intron_variant	Intron 2 of 19	ENST00000307790.8	NP_115580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC2	ENST00000307790.8	c.81+2261T>C		intron_variant	Intron 2 of 19	1	NM_032204.5	ENSP00000305502.3

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

African (AFR) AF: 0.297 AC: 12291 AN: 41446

American (AMR) AF: 0.106 AC: 1627 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 215 AN: 3472

East Asian (EAS) AF: 0.0797 AC: 413 AN: 5182

South Asian (SAS) AF: 0.0992 AC: 479 AN: 4828

European-Finnish (FIN) AF: 0.0679 AC: 720 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3859 AN: 67990

Other (OTH) AF: 0.118 AC: 250 AN: 2116

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
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73394838; hg19: chr22-30225973;