NM_001039753.4:c.1933-61G>A

Variant names:

• chr2-54866705-G-A
• rs1961245
• NM_001039753.4:c.1933-61G>A

Variant summary

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

The NM_001039753.4(EML6):​c.1933-61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 845,580 control chromosomes in the GnomAD database, including 73,407 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 0.45 (16240 hom., cov: 32)
  • Exomes 𝑓: 0.40 (57167 hom.)
• Consequence: EML6 NM_001039753.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 8 publications found

Genes affected

EML6 (HGNC:35412): (EMAP like 6) Predicted to enable microtubule binding activity. Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039753.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML6	NM_001039753.4	MANE Select	c.1933-61G>A		intron	N/A	NP_001034842.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML6	ENST00000356458.8	TSL:5 MANE Select	c.1933-61G>A		intron	N/A	ENSP00000348842.6
	EML6	ENST00000493997.1	TSL:5	n.281-61G>A		intron	N/A
	EML6	ENST00000673912.1		n.1933-61G>A		intron	N/A	ENSP00000501234.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68112 AN: 151922 Hom.: 16222 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.440

GnomAD4 exome AF: 0.396 AC: 274347 AN: 693540 Hom.: 57167 AF XY: 0.402 AC XY: 144208 AN XY: 358838

African (AFR) AF: 0.614 AC: 10506 AN: 17102

American (AMR) AF: 0.413 AC: 9921 AN: 24046

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 6983 AN: 17548

East Asian (EAS) AF: 0.549 AC: 17545 AN: 31938

South Asian (SAS) AF: 0.559 AC: 27828 AN: 49800

European-Finnish (FIN) AF: 0.423 AC: 19112 AN: 45180

Middle Eastern (MID) AF: 0.458 AC: 1896 AN: 4142

European-Non Finnish (NFE) AF: 0.355 AC: 166927 AN: 470590

Other (OTH) AF: 0.411 AC: 13629 AN: 33194

GnomAD4 genome AF: 0.448 AC: 68181 AN: 152040 Hom.: 16240 Cov.: 32 AF XY: 0.453 AC XY: 33705 AN XY: 74330

African (AFR) AF: 0.597 AC: 24751 AN: 41468

American (AMR) AF: 0.414 AC: 6333 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2824 AN: 5172

South Asian (SAS) AF: 0.566 AC: 2728 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4672 AN: 10554

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24022 AN: 67950

Other (OTH) AF: 0.440 AC: 931 AN: 2114

Alfa AF: 0.390 Hom.: 8952

Bravo AF: 0.451

Asia WGS AF: 0.554 AC: 1925 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.16
DANN	Benign	0.19
PhyloP100		-1.0
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: rs1961245; hg19: chr2-55093842; COSMIC: COSV62863362;