rs7781309

chr7-152354105-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170606.3(KMT2C):c.250+4482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,046 control chromosomes in the GnomAD database, including 12,448 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 0.33 (12448 hom., cov: 32)
• Consequence: KMT2C NM_170606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.14

Genes affected

KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2C	NM_170606.3	c.250+4482A>G		intron_variant		ENST00000262189.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2C	ENST00000262189.11	c.250+4482A>G		intron_variant		1	NM_170606.3	P2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50418 AN: 151928 Hom.: 12412 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.332 AC: 50509 AN: 152046 Hom.: 12448 Cov.: 32 AF XY: 0.335 AC XY: 24881 AN XY: 74322

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.295

Alfa AF: 0.181 Hom.: 6265

Bravo AF: 0.344

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.40
Dann	Benign	0.24

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: rs7781309; hg19: chr7-152051190;