rs636589

Positions:

• chr18-6274886-A-C

Variant summary

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

The NM_001330559.2(L3MBTL4):​c.128-10848T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,106 control chromosomes in the GnomAD database, including 55,994 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 0.85 (55994 hom., cov: 31)
• Consequence: L3MBTL4 NM_001330559.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

Genes affected

L3MBTL4 (HGNC:26677): (L3MBTL histone methyl-lysine binding protein 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.128-10848T>G		intron_variant		ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.128-10848T>G		intron_variant		5	NM_001330559.2	ENSP00000318543	P4

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129817 AN: 151988 Hom.: 55933 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.854 AC: 129934 AN: 152106 Hom.: 55994 Cov.: 31 AF XY: 0.851 AC XY: 63272 AN XY: 74352

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.868

Alfa AF: 0.824 Hom.: 69842

Bravo AF: 0.864

Asia WGS AF: 0.783 AC: 2720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.48

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: rs636589; hg19: chr18-6274885;