Genetic Variant HRNR:p.Ser2088Ser (chr1-152215365-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

1 publications found

Variant links:

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]

HRNR links:

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

CCDST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	NM_001009931.3	MANE Select	c.6264C>T	p.Ser2088Ser	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
CCDST	NR_186761.1		n.353+25710G>A		intron	N/A
CCDST	NR_186762.1		n.179+25884G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6264C>T	p.Ser2088Ser	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
CCDST	ENST00000420707.5	TSL:5	n.158+25857G>A		intron	N/A
CCDST	ENST00000593011.5	TSL:4	n.296+46945G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

116

AN:

112504

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000254

AC:

AN:

220510

AF XY:

0.000222

show subpopulations

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 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.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

724350

show subpopulations

African (AFR)

AF:

0.00418

AC:

138

AN:

33016

American (AMR)

AF:

0.000292

AC:

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39410

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86044

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000280

AC:

AN:

1108786

Other (OTH)

AF:

0.000166

AC:

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00104

AC:

117

AN:

112616

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

54276

show subpopulations

African (AFR)

AF:

0.00389

AC:

109

AN:

28046

American (AMR)

AF:

0.000376

AC:

AN:

10652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2922

East Asian (EAS)

AF:

0.00

AC:

AN:

3358

South Asian (SAS)

AF:

0.00

AC:

AN:

3116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0000548

AC:

AN:

54788

Other (OTH)

AF:

0.000685

AC:

AN:

1460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.3

(source)

DANN

Benign

0.66

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over