rs403814

Variant names:

• chr18-6282594-A-C
• rs403814
• NM_001330559.2:c.128-18556T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-6282594-A-C
• chr18-6282594-A-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.128-18556T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,036 control chromosomes in the GnomAD database, including 7,242 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 (7242 hom., cov: 32)
• Consequence: L3MBTL4 NM_001330559.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.128-18556T>G		intron_variant	Intron 4 of 18	ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.128-18556T>G		intron_variant	Intron 4 of 18	5	NM_001330559.2	ENSP00000318543.7

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40814 AN: 151918 Hom.: 7209 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.269 AC: 40905 AN: 152036 Hom.: 7242 Cov.: 32 AF XY: 0.268 AC XY: 19906 AN XY: 74322

African (AFR) AF: 0.504 AC: 20877 AN: 41406

American (AMR) AF: 0.200 AC: 3059 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1227 AN: 5152

South Asian (SAS) AF: 0.200 AC: 964 AN: 4820

European-Finnish (FIN) AF: 0.147 AC: 1553 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11690 AN: 67982

Other (OTH) AF: 0.273 AC: 576 AN: 2112

Alfa AF: 0.211 Hom.: 11262

Bravo AF: 0.285

Asia WGS AF: 0.257 AC: 893 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	4.9
DANN	Benign	0.78
PhyloP100		-0.24
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: rs403814; hg19: chr18-6282593;