8-38120214-T-G

Variant names:

• chr8-38120214-T-G
• rs2517388
• NM_004674.5:c.948-718T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004674.5(ASH2L):​c.948-718T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,096 control chromosomes in the GnomAD database, including 5,073 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 0.24 (5073 hom., cov: 32)
• Consequence: ASH2L NM_004674.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 22 publications found

Genes affected

ASH2L (HGNC:744): (ASH2 like, histone lysine methyltransferase complex subunit) Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Contributes to histone methyltransferase activity (H3-K4 specific). Involved in histone H3-K4 methylation; positive regulation of cell population proliferation; and response to estrogen. Acts upstream of or within cellular response to DNA damage stimulus. Located in nucleus. Part of MLL3/4 complex and Set1C/COMPASS 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASH2L	NM_004674.5	c.948-718T>G		intron_variant	Intron 9 of 15	ENST00000343823.11	NP_004665.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASH2L	ENST00000343823.11	c.948-718T>G		intron_variant	Intron 9 of 15	1	NM_004674.5	ENSP00000340896.5

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36565 AN: 151978 Hom.: 5073 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.241 AC: 36602 AN: 152096 Hom.: 5073 Cov.: 32 AF XY: 0.247 AC XY: 18359 AN XY: 74344

African (AFR) AF: 0.298 AC: 12351 AN: 41502

American (AMR) AF: 0.248 AC: 3794 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3466

East Asian (EAS) AF: 0.631 AC: 3251 AN: 5156

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2688 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11879 AN: 67984

Other (OTH) AF: 0.224 AC: 471 AN: 2104

Alfa AF: 0.198 Hom.: 15619

Bravo AF: 0.241

Asia WGS AF: 0.412 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.20
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: rs2517388; hg19: chr8-37977732;