rs1539808

Positions:

• chr18-5978932-C-T

Variant summary

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

The NM_001330559.2(L3MBTL4):​c.1445-9370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,190 control chromosomes in the GnomAD database, including 852 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 0.077 (852 hom., cov: 32)
• Consequence: L3MBTL4 NM_001330559.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.1445-9370G>A		intron_variant		ENST00000317931.12	NP_001317488.1
LOC121725015	NR_172505.1	n.361-6071C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.1445-9370G>A		intron_variant		5	NM_001330559.2	ENSP00000318543	P4
	ENST00000659442.1	n.343-42410C>T		intron_variant, non_coding_transcript_variant
	ENST00000664630.1	n.332-6077C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11673 AN: 152070 Hom.: 843 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0770 AC: 11712 AN: 152190 Hom.: 852 Cov.: 32 AF XY: 0.0823 AC XY: 6126 AN XY: 74400

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0357 Hom.: 106

Bravo AF: 0.0764

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.49

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: rs1539808; hg19: chr18-5978931;