rs1771316

Positions:

• chr1-225493278-A-C
• chr1-225493278-A-G

Variant summary

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

The NM_018212.6(ENAH):​c.*4497T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,180 control chromosomes in the GnomAD database, including 66,794 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 0.94 (66792 hom., cov: 31)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.*4497T>G		3_prime_UTR_variant	14/14	ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.*4497T>G		3_prime_UTR_variant	14/14	1	NM_018212.6	P2
ENAH	ENST00000366844.7	c.*4497T>G		3_prime_UTR_variant	15/15	1		A2
ENAH	ENST00000696609.1	c.*4497T>G		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142389 AN: 152058 Hom.: 66742 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.944

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.936 AC: 142496 AN: 152176 Hom.: 66792 Cov.: 31 AF XY: 0.937 AC XY: 69686 AN XY: 74378

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.944

Alfa AF: 0.954 Hom.: 84496

Bravo AF: 0.934

Asia WGS AF: 0.928 AC: 3228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.82
DANN	Benign	0.49

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: rs1771316; hg19: chr1-225680980; COSMIC: COSV52866205; COSMIC: COSV52866205;