rs2274316

Variant names:

• chr1-156476450-C-A
• rs2274316
• NM_005920.4:c.876+44G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-156476450-C-A
• chr1-156476450-C-G
• chr1-156476450-C-T

Variant summary

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

The NM_005920.4(MEF2D):​c.876+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,601,862 control chromosomes in the GnomAD database, including 329,700 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 (24981 hom., cov: 32)
  • Exomes 𝑓: 0.64 (304719 hom.)
• Consequence: MEF2D NM_005920.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 47 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2D	NM_005920.4	c.876+44G>T		intron_variant	Intron 8 of 11	ENST00000348159.9	NP_005911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2D	ENST00000348159.9	c.876+44G>T		intron_variant	Intron 8 of 11	1	NM_005920.4	ENSP00000271555.5
MEF2D	ENST00000360595.7	c.855+562G>T		intron_variant	Intron 7 of 10	1		ENSP00000353803.3
MEF2D	ENST00000464356.6	c.852+562G>T		intron_variant	Intron 6 of 9	5		ENSP00000476788.1
MEF2D	ENST00000475587.2	n.*224+562G>T		intron_variant	Intron 6 of 8	5		ENSP00000477413.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83751 AN: 151994 Hom.: 24973 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.612

GnomAD2 exomes AF: 0.623 AC: 148448 AN: 238254 AF XY: 0.636

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.662

Gnomad EAS exome AF: 0.730

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.645 AC: 934684 AN: 1449750 Hom.: 304719 Cov.: 31 AF XY: 0.648 AC XY: 466972 AN XY: 720206

African (AFR) AF: 0.287 AC: 9574 AN: 33328

American (AMR) AF: 0.567 AC: 24599 AN: 43382

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 17150 AN: 25858

East Asian (EAS) AF: 0.720 AC: 28445 AN: 39528

South Asian (SAS) AF: 0.685 AC: 57886 AN: 84500

European-Finnish (FIN) AF: 0.581 AC: 30703 AN: 52824

Middle Eastern (MID) AF: 0.713 AC: 4102 AN: 5754

European-Non Finnish (NFE) AF: 0.656 AC: 724350 AN: 1104560

Other (OTH) AF: 0.631 AC: 37875 AN: 60016

GnomAD4 genome AF: 0.551 AC: 83774 AN: 152112 Hom.: 24981 Cov.: 32 AF XY: 0.552 AC XY: 41068 AN XY: 74376

African (AFR) AF: 0.297 AC: 12334 AN: 41476

American (AMR) AF: 0.597 AC: 9128 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2296 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3783 AN: 5174

South Asian (SAS) AF: 0.686 AC: 3310 AN: 4828

European-Finnish (FIN) AF: 0.573 AC: 6061 AN: 10572

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44874 AN: 67976

Other (OTH) AF: 0.617 AC: 1302 AN: 2110

Alfa AF: 0.633 Hom.: 105585

Bravo AF: 0.539

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.5
DANN	Benign	0.89
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2274316; hg19: chr1-156446242;