rs341173

Positions:

• chr18-6328137-C-A

Variant summary

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

The NM_001330559.2(L3MBTL4):​c.-90-16081G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,152 control chromosomes in the GnomAD database, including 7,514 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 0.27 (7514 hom., cov: 33)
• Consequence: L3MBTL4 NM_001330559.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.-90-16081G>T		intron_variant		ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.-90-16081G>T		intron_variant		5	NM_001330559.2	ENSP00000318543	P4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41665 AN: 152034 Hom.: 7480 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.274 AC: 41756 AN: 152152 Hom.: 7514 Cov.: 33 AF XY: 0.273 AC XY: 20291 AN XY: 74384

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.276

Alfa AF: 0.240 Hom.: 920

Bravo AF: 0.291

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.46

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: rs341173; hg19: chr18-6328136; COSMIC: COSV53124764; COSMIC: COSV53124764;