rs142767236

Variant names:

• chr8-22114880-C-G
• rs142767236
• NM_005144.5:c.*820G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-22114880-C-G
• chr8-22114880-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005144.5(HR):​c.*820G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,596 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (76 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (0 hom.)
• Consequence: HR NM_005144.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0360
• Publications: 1 publications found

Genes affected

HR (HGNC:5172): (HR lysine demethylase and nuclear receptor corepressor) This gene encodes a protein that is involved in hair growth. This protein functions as a transcriptional corepressor of multiple nuclear receptors, including thyroid hormone receptor, the retinoic acid receptor-related orphan receptors and the vitamin D receptors, and it interacts with histone deacetylases. The translation of this protein is modulated by a regulatory open reading frame (ORF) that exists upstream of the primary ORF. Mutations in this upstream ORF cause Marie Unna hereditary hypotrichosis (MUHH), an autosomal dominant form of genetic hair loss. Mutations in this gene also cause autosomal recessive congenital alopecia and atrichia with papular lesions, other diseases resulting in hair loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

HR Gene-Disease associations (from GenCC):

• alopecia universalis congenita

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• atrichia with papular lesions

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• hypotrichosis 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Marie Unna hereditary hypotrichosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-22114880-C-G is Benign according to our data. Variant chr8-22114880-C-G is described in ClinVar as Benign. ClinVar VariationId is 362459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005144.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HR	NM_005144.5	MANE Select	c.*820G>C		3_prime_UTR	Exon 19 of 19	NP_005135.2
	HR	NM_018411.4		c.*820G>C		3_prime_UTR	Exon 18 of 18	NP_060881.2	O43593-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HR	ENST00000381418.9	TSL:1 MANE Select	c.*820G>C		3_prime_UTR	Exon 19 of 19	ENSP00000370826.4	O43593-1
	HR	ENST00000680789.1		c.*820G>C		3_prime_UTR	Exon 20 of 20	ENSP00000505181.1	O43593-1
	HR	ENST00000312841.9	TSL:5	c.*820G>C		3_prime_UTR	Exon 18 of 18	ENSP00000326765.8	O43593-2

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3035 AN: 152220 Hom.: 76 Cov.: 33

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00388 AC: 1 AN: 258 Hom.: 0 Cov.: 0 AF XY: 0.00581 AC XY: 1 AN XY: 172

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 210

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome AF: 0.0199 AC: 3039 AN: 152338 Hom.: 76 Cov.: 33 AF XY: 0.0193 AC XY: 1440 AN XY: 74506

African (AFR) AF: 0.0555 AC: 2308 AN: 41576

American (AMR) AF: 0.0112 AC: 172 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4834

European-Finnish (FIN) AF: 0.00103 AC: 11 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68026

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.0224

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Alopecia universalis congenita (1)
-	-	1	Atrichia with papular lesions (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.56
PhyloP100		0.036
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: rs142767236; hg19: chr8-21972393;