rs341173

Variant names:

• chr18-6328137-C-A
• rs341173
• NM_001330559.2:c.-90-16081G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ENSG00000298557 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.-90-16081G>T		intron_variant	Intron 1 of 18	ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.-90-16081G>T		intron_variant	Intron 1 of 18	5	NM_001330559.2	ENSP00000318543.7

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

African (AFR) AF: 0.516 AC: 21410 AN: 41468

American (AMR) AF: 0.203 AC: 3106 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1067 AN: 5178

South Asian (SAS) AF: 0.199 AC: 960 AN: 4830

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12066 AN: 68004

Other (OTH) AF: 0.276 AC: 584 AN: 2114

Alfa AF: 0.249 Hom.: 1030

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
PhyloP100		0.096
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: rs341173; hg19: chr18-6328136; COSMIC: COSV53124764; COSMIC: COSV53124764;