rs144489730

Variant names:

• chr1-152215365-G-A
• rs144489730
• NM_001009931.3:c.6264C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-152215365-G-A
• chr1-152215365-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001009931.3(HRNR):​c.6264C>T​(p.Ser2088Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,568,592 control chromosomes in the GnomAD database, including 18 homozygotes. 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. S2088S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0010 (6 hom., cov: 16)
  • Exomes 𝑓: 0.00014 (12 hom.)
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRNR	NM_001009931.3	c.6264C>T	p.Ser2088Ser	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.6264C>T	p.Ser2088Ser	synonymous_variant	Exon 3 of 3	1	NM_001009931.3	ENSP00000357791.3

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 116 AN: 112504 Hom.: 6 Cov.: 16

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000547

Gnomad OTH AF: 0.000693

GnomAD3 exomes AF: 0.000254 AC: 56 AN: 220510 Hom.: 1 AF XY: 0.000222 AC XY: 27 AN XY: 121556

Gnomad AFR exome AF: 0.00279

Gnomad AMR exome AF: 0.000309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000501

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000135 AC: 197 AN: 1455976 Hom.: 12 Cov.: 35 AF XY: 0.000119 AC XY: 86 AN XY: 724350

Gnomad4 AFR exome AF: 0.00418

Gnomad4 AMR exome AF: 0.000292

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000280

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.00104 AC: 117 AN: 112616 Hom.: 6 Cov.: 16 AF XY: 0.00105 AC XY: 57 AN XY: 54276

Gnomad4 AFR AF: 0.00389

Gnomad4 AMR AF: 0.000376

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000548

Gnomad4 OTH AF: 0.000685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.66

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: rs144489730; hg19: chr1-152187841; COSMIC: COSV64262514;