chr1-155442246-C-T

Position:

• chr1-155442246-C-T

Variant summary

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

The NM_018489.3(ASH1L):​c.5087-3178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,712 control chromosomes in the GnomAD database, including 7,488 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 0.30 (7488 hom., cov: 29)
• Consequence: ASH1L NM_018489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

Genes affected

ASH1L (HGNC:19088): (ASH1 like histone lysine methyltransferase) This gene encodes a member of the trithorax group of transcriptional activators. The protein contains four AT hooks, a SET domain, a PHD-finger motif, and a bromodomain. It is localized to many small speckles in the nucleus, and also to cell-cell tight junctions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASH1L	NM_018489.3	c.5087-3178G>A		intron_variant		ENST00000392403.8	NP_060959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASH1L	ENST00000392403.8	c.5087-3178G>A		intron_variant		5	NM_018489.3	ENSP00000376204.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45606 AN: 151594 Hom.: 7470 Cov.: 29

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.301 AC: 45665 AN: 151712 Hom.: 7488 Cov.: 29 AF XY: 0.304 AC XY: 22535 AN XY: 74136

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.284

Alfa AF: 0.252 Hom.: 8865

Bravo AF: 0.311

Asia WGS AF: 0.507 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.28

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: rs11264371; hg19: chr1-155412037;