rs6001946

Positions:

• chr22-40507417-A-G
• chr22-40507417-A-T

Variant summary

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

The NM_020831.6(MRTFA):​c.242-44131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,918 control chromosomes in the GnomAD database, including 1,261 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 0.12 (1261 hom., cov: 30)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

Genes affected

MRTFA (HGNC:14334): (myocardin related transcription factor A) The protein encoded by this gene interacts with the transcription factor myocardin, a key regulator of smooth muscle cell differentiation. The encoded protein is predominantly nuclear and may help transduce signals from the cytoskeleton to the nucleus. This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.242-44131T>C		intron_variant		ENST00000355630.10	NP_065882.2
MRTFA	NM_001282661.3	c.242-44131T>C		intron_variant			NP_001269590.2
MRTFA	NM_001282662.3	c.242-44131T>C		intron_variant			NP_001269591.2
MRTFA	NM_001318139.2	c.46+26173T>C		intron_variant			NP_001305068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.242-44131T>C		intron_variant		1	NM_020831.6	ENSP00000347847

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18252 AN: 151800 Hom.: 1253 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18287 AN: 151918 Hom.: 1261 Cov.: 30 AF XY: 0.126 AC XY: 9319 AN XY: 74244

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0853 Hom.: 191

Bravo AF: 0.114

Asia WGS AF: 0.186 AC: 646 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	1.3
DANN	Benign	0.49

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: rs6001946; hg19: chr22-40903421;