Genetic Variant NM_001009931.3:c.7995C>T (chr1-152213634-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001009931.3(HRNR):c.7995C>T(p.Ser2665Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000057 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000085 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HRNR
NM_001009931.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.27

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 1-152213634-G-A is Benign according to our data. Variant chr1-152213634-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3388710.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.27 with no splicing effect.

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.7995C>T	p.Ser2665Ser	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
CCDST	NR_186761.1		n.353+23979G>A		intron	N/A
CCDST	NR_186762.1		n.179+24153G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	ENST00000368801.4	TSL:1 MANE Select	c.7995C>T	p.Ser2665Ser	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
CCDST	ENST00000420707.5	TSL:5	n.158+24126G>A		intron	N/A
CCDST	ENST00000593011.5	TSL:4	n.296+45214G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000708

AC:

AN:

70598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000305

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000612

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0293

AC:

1735

AN:

59290

AF XY:

0.0300

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.00820

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00264

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.0351

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000849

AC:

105

AN:

1237164

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

621458

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000693

AC:

AN:

28876

American (AMR)

AF:

0.000169

AC:

AN:

41504

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

22842

East Asian (EAS)

AF:

0.00

AC:

AN:

39370

South Asian (SAS)

AF:

0.0000362

AC:

AN:

82904

European-Finnish (FIN)

AF:

0.000105

AC:

AN:

47838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4284

European-Non Finnish (NFE)

AF:

0.0000840

AC:

AN:

916852

Other (OTH)

AF:

0.0000759

AC:

AN:

52694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.249

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000566

AC:

AN:

70658

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33664

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000103

AC:

AN:

19354

American (AMR)

AF:

0.00

AC:

AN:

6304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1714

East Asian (EAS)

AF:

0.00

AC:

AN:

3266

South Asian (SAS)

AF:

0.00

AC:

AN:

2096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

32656

Other (OTH)

AF:

0.00

AC:

AN:

878

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00291

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.48

(source)

DANN

Benign

0.65

PhyloP100

-3.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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