6-100731478-T-G

Variant names:

• chr6-100731478-T-G
• rs6909880
• NM_006828.4:c.1738-5775A>C

Variant summary

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

The NM_006828.4(ASCC3):​c.1738-5775A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,074 control chromosomes in the GnomAD database, including 16,867 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 0.47 (16867 hom., cov: 33)
• Consequence: ASCC3 NM_006828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

ASCC3 (HGNC:18697): (activating signal cointegrator 1 complex subunit 3) This gene encodes a protein that belongs to a family of helicases that are involved in the ATP-dependent unwinding of nucleic acid duplexes. The encoded protein is the largest subunit of the activating signal cointegrator 1 complex that is involved in DNA repair and resistance to alkylation damage. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCC3	NM_006828.4	c.1738-5775A>C		intron_variant	Intron 10 of 41	ENST00000369162.7	NP_006819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCC3	ENST00000369162.7	c.1738-5775A>C		intron_variant	Intron 10 of 41	5	NM_006828.4	ENSP00000358159.2
ASCC3	ENST00000522650.5	c.1738-5775A>C		intron_variant	Intron 10 of 12	1		ENSP00000430769.1
ASCC3	ENST00000324696.8	n.*1440-5775A>C		intron_variant	Intron 9 of 19	2		ENSP00000320252.4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71243 AN: 151956 Hom.: 16853 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.469 AC: 71284 AN: 152074 Hom.: 16867 Cov.: 33 AF XY: 0.469 AC XY: 34877 AN XY: 74320

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.450

Alfa AF: 0.376 Hom.: 1543

Bravo AF: 0.456

Asia WGS AF: 0.443 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6909880; hg19: chr6-101179354; COSMIC: COSV61226951;