rs12457649

Variant names:

• chr18-6097486-T-C
• rs12457649
• NM_001330559.2:c.1200-3958A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330559.2(L3MBTL4):​c.1200-3958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,092 control chromosomes in the GnomAD database, including 32,939 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 0.63 (32939 hom., cov: 31)
• Consequence: L3MBTL4 NM_001330559.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 5 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]

ENSG00000266846 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330559.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL4	NM_001330559.2	MANE Select	c.1200-3958A>G		intron	N/A	NP_001317488.1	F8W9S8
	L3MBTL4	NM_001365770.2		c.1200-3958A>G		intron	N/A	NP_001352699.1	Q8NA19-1
	L3MBTL4	NM_173464.4		c.1200-3958A>G		intron	N/A	NP_775735.2	Q8NA19-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL4	ENST00000317931.12	TSL:5 MANE Select	c.1200-3958A>G		intron	N/A	ENSP00000318543.7	F8W9S8
	L3MBTL4	ENST00000400104.7	TSL:1	c.1200-3958A>G		intron	N/A	ENSP00000382975.3	Q8NA19-2
	L3MBTL4	ENST00000955913.1		c.1233-3958A>G		intron	N/A	ENSP00000625972.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95701 AN: 151974 Hom.: 32872 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.630 AC: 95830 AN: 152092 Hom.: 32939 Cov.: 31 AF XY: 0.629 AC XY: 46767 AN XY: 74358

African (AFR) AF: 0.908 AC: 37692 AN: 41518

American (AMR) AF: 0.673 AC: 10288 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3712 AN: 5158

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4812

European-Finnish (FIN) AF: 0.391 AC: 4137 AN: 10582

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32956 AN: 67952

Other (OTH) AF: 0.642 AC: 1356 AN: 2112

Alfa AF: 0.540 Hom.: 38811

Bravo AF: 0.666

Asia WGS AF: 0.667 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.099
DANN	Benign	0.21
PhyloP100		-2.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12457649;

hg19: chr18-6097485;