1-152214519-G-T

Variant names:

• chr1-152214519-G-T
• rs762094151
• NM_001009931.3:c.7110C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001009931.3(HRNR):​c.7110C>A​(p.His2370Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H2370H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 59)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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]

FLG-AS1 (HGNC:):

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05964914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3	c.7110C>A	p.His2370Gln	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.7110C>A	p.His2370Gln	missense_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3

Frequencies

GnomAD3 genomes Cov.: 59

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1460780 Hom.: 0 Cov.: 208 AF XY: 0.00000275 AC XY: 2 AN XY: 726720

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 59

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.077
DANN	Benign	0.49
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.021
Sift	Benign	0.033	D
Sift4G	Benign	0.39	T
Polyphen		0.16	B
Vest4		0.21
MutPred		0.20		Loss of catalytic residue at H2370 (P = 0.0648);
MVP		0.20
ClinPred		0.062	T
GERP RS		-2.7
Varity_R		0.040
gMVP		0.035

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

Publications

LitVar

Other links and lift over

dbSNP: rs762094151; hg19: chr1-152186995;