NM_033546.4:c.-15-4332T>C

Variant names:

• chr18-3268552-T-C
• rs1791067
• NM_033546.4:c.-15-4332T>C

Variant summary

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

The NM_033546.4(MYL12B):​c.-15-4332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,100 control chromosomes in the GnomAD database, including 6,239 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 0.28 (6239 hom., cov: 32)
• Consequence: MYL12B NM_033546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 5 publications found

Genes affected

MYL12B (HGNC:29827): (myosin light chain 12B) The activity of nonmuscle myosin II (see MYH9; MIM 160775) is regulated by phosphorylation of a regulatory light chain, such as MRLC2. This phosphorylation results in higher MgATPase activity and the assembly of myosin II filaments (Iwasaki et al., 2001 [PubMed 11942626]).[supplied by OMIM, Mar 2008]

ENSG00000301728 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033546.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL12B	NM_033546.4	MANE Select	c.-15-4332T>C		intron	N/A	NP_291024.1
	MYL12B	NM_001144944.1		c.-15-4332T>C		intron	N/A	NP_001138416.1
	MYL12B	NM_001144945.1		c.-15-4332T>C		intron	N/A	NP_001138417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL12B	ENST00000237500.10	TSL:1 MANE Select	c.-15-4332T>C		intron	N/A	ENSP00000237500.5
	MYL12B	ENST00000400175.9	TSL:3	c.-15-4332T>C		intron	N/A	ENSP00000383037.5
	MYL12B	ENST00000581193.5	TSL:3	c.-15-4332T>C		intron	N/A	ENSP00000463559.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42277 AN: 151980 Hom.: 6227 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.278 AC: 42332 AN: 152100 Hom.: 6239 Cov.: 32 AF XY: 0.280 AC XY: 20783 AN XY: 74356

African (AFR) AF: 0.351 AC: 14533 AN: 41452

American (AMR) AF: 0.175 AC: 2674 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1718 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1487 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3172 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17259 AN: 67986

Other (OTH) AF: 0.250 AC: 528 AN: 2116

Alfa AF: 0.254 Hom.: 15987

Bravo AF: 0.267

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		0.46
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: rs1791067; hg19: chr18-3268550; COSMIC: COSV52899139;