chr15-48141297-A-G

Variant names:

• chr15-48141297-A-G
• rs2470102
• NM_016132.5:c.*1611T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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]

SLC24A5 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016132.5. 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
	MYEF2	NM_016132.5	MANE Select	c.*1611T>C		3_prime_UTR	Exon 17 of 17	NP_057216.3
	SLC24A5	NM_205850.3	MANE Select	c.1180+83A>G		intron	N/A	NP_995322.1	Q71RS6-1
	MYEF2	NM_001301210.2		c.*1611T>C		3_prime_UTR	Exon 16 of 16	NP_001288139.2	A0A0A0MQW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYEF2	ENST00000324324.12	TSL:1 MANE Select	c.*1611T>C		3_prime_UTR	Exon 17 of 17	ENSP00000316950.7	A0A0A0MR39
	SLC24A5	ENST00000341459.8	TSL:1 MANE Select	c.1180+83A>G		intron	N/A	ENSP00000341550.3	Q71RS6-1
	SLC24A5	ENST00000449382.2	TSL:1	c.1000+83A>G		intron	N/A	ENSP00000389966.2	Q71RS6-2

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

African (AFR) AF: 0.820 AC: 19456 AN: 23726

American (AMR) AF: 0.363 AC: 13058 AN: 35994

Ashkenazi Jewish (ASJ) AF: 0.00552 AC: 117 AN: 21180

East Asian (EAS) AF: 0.739 AC: 26055 AN: 35234

South Asian (SAS) AF: 0.173 AC: 12234 AN: 70916

European-Finnish (FIN) AF: 0.00661 AC: 323 AN: 48854

Middle Eastern (MID) AF: 0.0340 AC: 165 AN: 4846

European-Non Finnish (NFE) AF: 0.00823 AC: 6176 AN: 750036

Other (OTH) AF: 0.129 AC: 5820 AN: 45200

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

African (AFR) AF: 0.799 AC: 33132 AN: 41484

American (AMR) AF: 0.267 AC: 4089 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3781 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4812

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00893 AC: 607 AN: 67984

Other (OTH) AF: 0.227 AC: 480 AN: 2112

Alfa AF: 0.130 Hom.: 6651

Bravo AF: 0.330

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.63
PhyloP100		-2.0
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: rs2470102; hg19: chr15-48433494;