1-152214975-C-T

Variant names:

• chr1-152214975-C-T
• rs144369469
• NM_001009931.3:c.6654G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001009931.3(HRNR):​c.6654G>A​(p.Ser2218Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. S2218S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.011 (4 hom., cov: 37)
  • Exomes 𝑓: 0.011 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3	c.6654G>A	p.Ser2218Ser	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.6654G>A	p.Ser2218Ser	synonymous_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1589 AN: 142418 Hom.: 4 Cov.: 37

Gnomad AFR AF: 0.00334

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00455

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0118

GnomAD3 exomes AF: 0.0148 AC: 1174 AN: 79386 Hom.: 18 AF XY: 0.0150 AC XY: 580 AN XY: 38600

Gnomad AFR exome AF: 0.00374

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.0123

Gnomad SAS exome AF: 0.0322

Gnomad FIN exome AF: 0.00603

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0170

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0109 AC: 15377 AN: 1412758 Hom.: 15 Cov.: 119 AF XY: 0.0115 AC XY: 8047 AN XY: 702422

Gnomad4 AFR exome AF: 0.00306

Gnomad4 AMR exome AF: 0.00728

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0305

Gnomad4 SAS exome AF: 0.0253

Gnomad4 FIN exome AF: 0.00440

Gnomad4 NFE exome AF: 0.00979

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0111 AC: 1585 AN: 142544 Hom.: 4 Cov.: 37 AF XY: 0.0111 AC XY: 775 AN XY: 69692

Gnomad4 AFR AF: 0.00332

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.0161

Gnomad4 SAS AF: 0.0316

Gnomad4 FIN AF: 0.00455

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0112

Alfa AF: 0.00636 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.62

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: rs144369469; hg19: chr1-152187451;