rs3790455

Variant names:

• chr1-156486509-C-T
• rs3790455
• NM_005920.4:c.-138-3079G>A

Variant summary

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

The NM_005920.4(MEF2D):​c.-138-3079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,076 control chromosomes in the GnomAD database, including 25,131 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 0.55 (25131 hom., cov: 32)
• Consequence: MEF2D NM_005920.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 24 publications found

Genes affected

MEF2D (HGNC:6997): (myocyte enhancer factor 2D) This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005920.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2D	NM_005920.4	MANE Select	c.-138-3079G>A		intron	N/A	NP_005911.1	Q14814-1
	MEF2D	NM_001271629.2		c.-126-3091G>A		intron	N/A	NP_001258558.1	Q14814-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2D	ENST00000348159.9	TSL:1 MANE Select	c.-138-3079G>A		intron	N/A	ENSP00000271555.5	Q14814-1
	MEF2D	ENST00000360595.7	TSL:1	c.-126-3091G>A		intron	N/A	ENSP00000353803.3	Q14814-4
	MEF2D	ENST00000970822.1		c.-418G>A		5_prime_UTR	Exon 3 of 13	ENSP00000640881.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83996 AN: 151958 Hom.: 25122 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.552 AC: 84020 AN: 152076 Hom.: 25131 Cov.: 32 AF XY: 0.554 AC XY: 41150 AN XY: 74336

African (AFR) AF: 0.299 AC: 12395 AN: 41452

American (AMR) AF: 0.598 AC: 9155 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2298 AN: 3472

East Asian (EAS) AF: 0.730 AC: 3782 AN: 5180

South Asian (SAS) AF: 0.686 AC: 3308 AN: 4822

European-Finnish (FIN) AF: 0.575 AC: 6073 AN: 10568

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45023 AN: 67966

Other (OTH) AF: 0.617 AC: 1301 AN: 2108

Alfa AF: 0.632 Hom.: 88434

Bravo AF: 0.540

Asia WGS AF: 0.696 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.60
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: rs3790455; hg19: chr1-156456301;