1-156476450-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005920.4(MEF2D):​c.876+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451400 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721004

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 84560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105948

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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;