15-48141297-A-G

Variant summary

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

The NM_016132.5(MYEF2):c.*1611T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,188,128 control chromosomes in the GnomAD database, including 39,059 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 (15737 hom., cov: 32)
  • Exomes 𝑓: 0.081 (23322 hom.)
• Consequence: MYEF2 NM_016132.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

Genes affected

MYEF2 (HGNC:17940): (myelin expression factor 2) Enables RNA binding activity. Involved in myotube differentiation and neuron differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYEF2	NM_016132.5	c.*1611T>C		3_prime_UTR_variant	17/17	ENST00000324324.12
SLC24A5	NM_205850.3	c.1180+83A>G		intron_variant		ENST00000341459.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYEF2	ENST00000324324.12	c.*1611T>C		3_prime_UTR_variant	17/17	1	NM_016132.5	P4
SLC24A5	ENST00000341459.8	c.1180+83A>G		intron_variant		1	NM_205850.3	P1
SLC24A5	ENST00000449382.2	c.1000+83A>G		intron_variant		1
MYEF2	ENST00000558289.5	n.2651T>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43054 AN: 152024 Hom.: 15662 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00893

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.0805 AC: 83404 AN: 1035986 Hom.: 23322 Cov.: 13 AF XY: 0.0788 AC XY: 41620 AN XY: 528246

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.00552

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.00661

Gnomad4 NFE exome AF: 0.00823

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.284 AC: 43199 AN: 152142 Hom.: 15737 Cov.: 32 AF XY: 0.283 AC XY: 21064 AN XY: 74404

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.00893

Gnomad4 OTH AF: 0.227

Alfa AF: 0.0919 Hom.: 3568

Bravo AF: 0.330

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.48
Dann	Benign	0.63

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: rs2470102; hg19: chr15-48433494;