1-152218471-C-T

Variant names:

• chr1-152218471-C-T
• rs142424978
• NM_001009931.3:c.3158G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001009931.3(HRNR):​c.3158G>A​(p.Arg1053Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,612,842 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0051 (21 hom.)
• Consequence: HRNR NM_001009931.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.264
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005783081).
• BP6: Variant 1-152218471-C-T is Benign according to our data. Variant chr1-152218471-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009931.3. 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
	HRNR	NM_001009931.3	MANE Select	c.3158G>A	p.Arg1053Gln	missense	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+28816C>T		intron	N/A
	CCDST	NR_186762.1		n.179+28990C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.3158G>A	p.Arg1053Gln	missense	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+28963C>T		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+50051C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 568 AN: 150976 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00105

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00704

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00528

Gnomad OTH AF: 0.00822

GnomAD2 exomes AF: 0.00302 AC: 760 AN: 251414 AF XY: 0.00302

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00407

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00506 AC: 7391 AN: 1461748 Hom.: 21 Cov.: 122 AF XY: 0.00485 AC XY: 3524 AN XY: 727176

African (AFR) AF: 0.000597 AC: 20 AN: 33474

American (AMR) AF: 0.00369 AC: 165 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39678

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86236

European-Finnish (FIN) AF: 0.00341 AC: 182 AN: 53410

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00604 AC: 6719 AN: 1111962

Other (OTH) AF: 0.00464 AC: 280 AN: 60368

GnomAD4 genome AF: 0.00376 AC: 568 AN: 151094 Hom.: 1 Cov.: 31 AF XY: 0.00370 AC XY: 273 AN XY: 73814

African (AFR) AF: 0.00105 AC: 43 AN: 40990

American (AMR) AF: 0.00703 AC: 107 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5004

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00360 AC: 38 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00528 AC: 358 AN: 67818

Other (OTH) AF: 0.00813 AC: 17 AN: 2090

Alfa AF: 0.00315 Hom.: 0

Bravo AF: 0.00370

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00617 AC: 53

ExAC AF: 0.00256 AC: 311

EpiCase AF: 0.00442

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.64
DEOGEN2	Benign	0.014	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.76	N
PhyloP100		-0.26
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.012
Sift	Benign	0.16	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.047
MVP		0.19
ClinPred		0.0012	T
GERP RS		-2.6
Varity_R		0.024
gMVP		0.0097
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: rs142424978; hg19: chr1-152190947; COSMIC: COSV106108872;