1-152216385-C-T

Variant names:

• chr1-152216385-C-T
• rs201735593
• NM_001009931.3:c.5244G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001009931.3(HRNR):​c.5244G>A​(p.Ser1748Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 144,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S1748S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 55)
  • Exomes 𝑓: 0.000072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3	c.5244G>A	p.Ser1748Ser	synonymous_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.5244G>A	p.Ser1748Ser	synonymous_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3

Frequencies

GnomAD3 genomes AF: 0.000111 AC: 16 AN: 144076 Hom.: 0 Cov.: 55

Gnomad AFR AF: 0.000104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000728

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000235

Gnomad FIN AF: 0.0000972

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000165 AC: 1 AN: 60516 Hom.: 0 AF XY: 0.0000330 AC XY: 1 AN XY: 30296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000724 AC: 105 AN: 1451256 Hom.: 0 Cov.: 112 AF XY: 0.0000706 AC XY: 51 AN XY: 722208

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000788

Gnomad4 OTH exome AF: 0.0000501

GnomAD4 genome AF: 0.000118 AC: 17 AN: 144170 Hom.: 0 Cov.: 55 AF XY: 0.000157 AC XY: 11 AN XY: 70080

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.0000728

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000236

Gnomad4 FIN AF: 0.0000972

Gnomad4 NFE AF: 0.000135

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.58

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: rs201735593; hg19: chr1-152188861; COSMIC: COSV64261059;