rs4930561

Positions:

• chr11-68164294-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KMT5B	NM_017635.5	c.1174+2688C>T		intron_variant		ENST00000304363.9	NP_060105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT5B	ENST00000304363.9	c.1174+2688C>T		intron_variant		5	NM_017635.5	ENSP00000305899	P1

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

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.553

Alfa AF: 0.514 Hom.: 41670

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

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: rs4930561; hg19: chr11-67931761;