11-69295926-T-C

Variant names:

• chr11-69295926-T-C
• rs7103126
• NM_001293291.2:c.476T>C

Variant summary

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

The NM_001293291.2(MYEOV):​c.476T>C​(p.Val159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,613,900 control chromosomes in the GnomAD database, including 54,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (14300 hom., cov: 32)
  • Exomes 𝑓: 0.21 (40335 hom.)
• Consequence: MYEOV NM_001293291.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29
• Publications: 31 publications found

Genes affected

MYEOV (HGNC:7563): (myeloma overexpressed)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.2649878E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293291.2. 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
	MYEOV	NM_001293291.2	MANE Select	c.476T>C	p.Val159Ala	missense	Exon 3 of 3	NP_001280220.1	Q96EZ4
	MYEOV	NM_138768.4		c.476T>C	p.Val159Ala	missense	Exon 3 of 3	NP_620123.2
	MYEOV	NM_001293294.2		c.302T>C	p.Val101Ala	missense	Exon 2 of 2	NP_001280223.1	F5H0B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYEOV	ENST00000441339.3	TSL:2 MANE Select	c.476T>C	p.Val159Ala	missense	Exon 3 of 3	ENSP00000412482.2	Q96EZ4
	MYEOV	ENST00000308946.3	TSL:1	c.476T>C	p.Val159Ala	missense	Exon 3 of 3	ENSP00000308330.3	Q96EZ4
	MYEOV	ENST00000535653.1	TSL:1	n.1107T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53892 AN: 151892 Hom.: 14251 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.262 AC: 65917 AN: 251404 AF XY: 0.258

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.207 AC: 302402 AN: 1461890 Hom.: 40335 Cov.: 34 AF XY: 0.210 AC XY: 153020 AN XY: 727244

African (AFR) AF: 0.765 AC: 25621 AN: 33480

American (AMR) AF: 0.181 AC: 8082 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5624 AN: 26136

East Asian (EAS) AF: 0.440 AC: 17470 AN: 39700

South Asian (SAS) AF: 0.361 AC: 31156 AN: 86258

European-Finnish (FIN) AF: 0.195 AC: 10433 AN: 53420

Middle Eastern (MID) AF: 0.263 AC: 1519 AN: 5768

European-Non Finnish (NFE) AF: 0.169 AC: 187626 AN: 1112008

Other (OTH) AF: 0.246 AC: 14871 AN: 60396

GnomAD4 genome AF: 0.355 AC: 53999 AN: 152010 Hom.: 14300 Cov.: 32 AF XY: 0.356 AC XY: 26478 AN XY: 74294

African (AFR) AF: 0.743 AC: 30793 AN: 41446

American (AMR) AF: 0.229 AC: 3503 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2236 AN: 5136

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2055 AN: 10588

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12002 AN: 67950

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.250 Hom.: 22812

Bravo AF: 0.367

TwinsUK AF: 0.161 AC: 598

ALSPAC AF: 0.179 AC: 689

ESP6500AA AF: 0.722 AC: 3177

ESP6500EA AF: 0.176 AC: 1513

ExAC AF: 0.277 AC: 33588

Asia WGS AF: 0.453 AC: 1577 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.069
DANN	Benign	0.20
DEOGEN2	Benign	0.00047	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.011
Polyphen		0.0	B
Vest4		0.036
MPC		0.078
ClinPred		0.0036	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7103126; hg19: chr11-69063393; COSMIC: COSV58293691; COSMIC: COSV58293691;