rs12457649

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.1200-3958A>G		intron_variant	Intron 14 of 18	ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.1200-3958A>G		intron_variant	Intron 14 of 18	5	NM_001330559.2	ENSP00000318543.7
L3MBTL4	ENST00000400104.7	c.1200-3958A>G		intron_variant	Intron 14 of 16	1		ENSP00000382975.3
L3MBTL4	ENST00000400105.6	c.1200-3958A>G		intron_variant	Intron 14 of 19	2		ENSP00000382976.2
ENSG00000266846	ENST00000659442.1	n.1423+8136T>C		intron_variant	Intron 7 of 7

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

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.642

Alfa AF: 0.526 Hom.: 28961

Bravo AF: 0.666

Asia WGS AF: 0.667 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs12457649; hg19: chr18-6097485;