chr1-236409068-TAAAA-T

Variant names:

• chr1-236409068-TAAAA-T
• rs772223735
• NM_145861.4:c.62-132_62-129delAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_145861.4(EDARADD):​c.62-132_62-129delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 333,084 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000343 (70/203972) while in subpopulation AMR AF= 0.000561 (4/7124). AF 95% confidence interval is 0.000265. There are 0 homozygotes in gnomad4_exome. There are 30 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-132_62-129delAAAA		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-132_32-129delAAAA		intron_variant	Intron 1 of 5		NP_542776.1
EDARADD	NM_001422628.1	c.-5-132_-5-129delAAAA		intron_variant	Intron 3 of 7		NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.62-147_62-144delAAAA		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.0000155 AC: 2 AN: 129112 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000166

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000343 AC: 70 AN: 203972 Hom.: 0 AF XY: 0.000280 AC XY: 30 AN XY: 107086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000561

Gnomad4 ASJ exome AF: 0.000338

Gnomad4 EAS exome AF: 0.000381

Gnomad4 SAS exome AF: 0.000425

Gnomad4 FIN exome AF: 0.000254

Gnomad4 NFE exome AF: 0.000346

Gnomad4 OTH exome AF: 0.000358

GnomAD4 genome AF: 0.0000155 AC: 2 AN: 129112 Hom.: 0 Cov.: 28 AF XY: 0.0000162 AC XY: 1 AN XY: 61772

Gnomad4 AFR AF: 0.0000287

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000166

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772223735; hg19: chr1-236572368;