1-152213599-C-A

Variant names:

• chr1-152213599-C-A
• rs201827906
• NM_001009931.3:c.8030G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001009931.3(HRNR):​c.8030G>T​(p.Arg2677Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2677P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

Genes affected

HRNR (HGNC:20846): (hornerin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Involved in cell envelope organization and establishment of skin barrier. Located in cornified envelope; keratohyalin granule; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.091379225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3	c.8030G>T	p.Arg2677Leu	missense_variant	Exon 3 of 3	ENST00000368801.4	NP_001009931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRNR	ENST00000368801.4	c.8030G>T	p.Arg2677Leu	missense_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1094524 Hom.: 0 Cov.: 31 AF XY: 0.00000182 AC XY: 1 AN XY: 549672

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25076

American (AMR) AF: 0.00 AC: 0 AN: 30810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18644

East Asian (EAS) AF: 0.00 AC: 0 AN: 36034

South Asian (SAS) AF: 0.00 AC: 0 AN: 72228

European-Finnish (FIN) AF: 0.0000221 AC: 1 AN: 45178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3820

European-Non Finnish (NFE) AF: 0.00000245 AC: 2 AN: 816000

Other (OTH) AF: 0.00 AC: 0 AN: 46734

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0556734), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 10

ExAC AF: 0.00000973 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.61
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.015
Sift	Benign	0.052	T
Sift4G	Uncertain	0.058	T
Polyphen		0.10	B
Vest4		0.23
MutPred		0.31		Loss of MoRF binding (P = 0.0021);
MVP		0.25
ClinPred		0.063	T
GERP RS		-0.93
Varity_R		0.057
gMVP		0.036
Mutation Taster		=100/0	polymorphism

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: rs201827906; hg19: chr1-152186075;