rs6751

Positions:

• chr1-225494858-G-A

Variant summary

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

The NM_018212.6(ENAH):​c.*2917C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,504 control chromosomes in the GnomAD database, including 33,461 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 0.66 (33367 hom., cov: 32)
  • Exomes 𝑓: 0.67 (94 hom.)
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAH	NM_018212.6	c.*2917C>T		3_prime_UTR_variant	14/14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.*2917C>T		3_prime_UTR_variant	14/14	1	NM_018212.6	ENSP00000355808	P2
ENAH	ENST00000366844.7	c.*2917C>T		3_prime_UTR_variant	15/15	1		ENSP00000355809	A2
ENAH	ENST00000696609.1	c.*2917C>T		3_prime_UTR_variant	12/12			ENSP00000512753

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100185 AN: 151958 Hom.: 33375 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.671 AC: 287 AN: 428 Hom.: 94 Cov.: 0 AF XY: 0.676 AC XY: 173 AN XY: 256

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.659 AC: 100213 AN: 152076 Hom.: 33367 Cov.: 32 AF XY: 0.655 AC XY: 48705 AN XY: 74356

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.679

Alfa AF: 0.681 Hom.: 11545

Bravo AF: 0.661

Asia WGS AF: 0.568 AC: 1974 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.75

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: rs6751; hg19: chr1-225682560; COSMIC: COSV52866210; COSMIC: COSV52866210;