rs4930561

Variant names:

• chr11-68164294-G-A
• rs4930561
• NM_017635.5:c.1174+2688C>T

Variant summary

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

The NM_017635.5(KMT5B):​c.1174+2688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,012 control chromosomes in the GnomAD database, including 22,497 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 0.54 (22497 hom., cov: 32)
• Consequence: KMT5B NM_017635.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 19 publications found

Genes affected

KMT5B (HGNC:24283): (lysine methyltransferase 5B) This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). The function of this gene has not been determined. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

KMT5B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 51

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT5B	NM_017635.5	c.1174+2688C>T		intron_variant	Intron 10 of 10	ENST00000304363.9	NP_060105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMT5B	ENST00000304363.9	c.1174+2688C>T		intron_variant	Intron 10 of 10	5	NM_017635.5	ENSP00000305899.4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82134 AN: 151894 Hom.: 22455 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.541 AC: 82225 AN: 152012 Hom.: 22497 Cov.: 32 AF XY: 0.548 AC XY: 40716 AN XY: 74292

African (AFR) AF: 0.550 AC: 22796 AN: 41432

American (AMR) AF: 0.635 AC: 9695 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1885 AN: 3464

East Asian (EAS) AF: 0.666 AC: 3448 AN: 5176

South Asian (SAS) AF: 0.687 AC: 3304 AN: 4810

European-Finnish (FIN) AF: 0.523 AC: 5530 AN: 10566

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33663 AN: 67966

Other (OTH) AF: 0.553 AC: 1168 AN: 2114

Alfa AF: 0.516 Hom.: 90353

Bravo AF: 0.551

Asia WGS AF: 0.673 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.29
PhyloP100		-0.31
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: rs4930561; hg19: chr11-67931761;