1-236483331-G-A

Position:

• chr1-236483331-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000334232.9(EDARADD):​c.*682G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,591,148 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (99 hom.)
• Consequence: EDARADD ENST00000334232.9 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.72

Genes affected

EDARADD (HGNC:14341): (EDAR associated via death domain) This gene was identified by its association with ectodermal dysplasia, a genetic disorder characterized by defective development of hair, teeth, and eccrine sweat glands. The protein encoded by this gene is a death domain-containing protein, and is found to interact with EDAR, a death domain receptor known to be required for the development of hair, teeth and other ectodermal derivatives. This protein and EDAR are coexpressed in epithelial cells during the formation of hair follicles and teeth. Through its interaction with EDAR, this protein acts as an adaptor, and links the receptor to downstream signaling pathways. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ENO1P1 (HGNC:3352): (enolase 1 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-236483331-G-A is Benign according to our data. Variant chr1-236483331-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 296464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.*682G>A		3_prime_UTR_variant	6/6	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4	c.*682G>A		3_prime_UTR_variant	6/6		NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.*682G>A		3_prime_UTR_variant	6/6	1	NM_145861.4	ENSP00000335076
ENO1P1	ENST00000366587.4	n.167G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3225 AN: 152128 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00211 AC: 3042 AN: 1438902 Hom.: 99 Cov.: 29 AF XY: 0.00189 AC XY: 1358 AN XY: 716640

Gnomad4 AFR exome AF: 0.0753

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.0213 AC: 3238 AN: 152246 Hom.: 123 Cov.: 32 AF XY: 0.0206 AC XY: 1537 AN XY: 74444

Gnomad4 AFR AF: 0.0739

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.00403 Hom.: 3

Bravo AF: 0.0250

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.0
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61740486; hg19: chr1-236646631;