Genetic Variant HRNR:p.Gly2711Gly (chr1-152213496-A-T) – 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.8133T>A(p.Gly2711Gly) 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 0.0 ( 0 hom., cov: 12)

Exomes 𝑓: 0.0 ( 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: -5.72

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP6

Variant 1-152213496-A-T is Benign according to our data. Variant chr1-152213496-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388750.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.72 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.8133T>A	p.Gly2711Gly	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
CCDST	NR_186761.1		n.353+23841A>T		intron	N/A
CCDST	NR_186762.1		n.179+24015A>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	ENST00000368801.4	TSL:1 MANE Select	c.8133T>A	p.Gly2711Gly	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
CCDST	ENST00000420707.5	TSL:5	n.158+23988A>T		intron	N/A
CCDST	ENST00000593011.5	TSL:4	n.296+45076A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98056

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000107

AC:

AN:

186056

AF XY:

0.00000987

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1267722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

635876

African (AFR)

AF:

0.00

AC:

AN:

30048

American (AMR)

AF:

0.00

AC:

AN:

43004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23904

East Asian (EAS)

AF:

0.00

AC:

AN:

39350

South Asian (SAS)

AF:

0.00

AC:

AN:

83536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4386

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

939388

Other (OTH)

AF:

0.00

AC:

AN:

54170

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

98056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46736

African (AFR)

AF:

0.00

AC:

AN:

27190

American (AMR)

AF:

0.00

AC:

AN:

9388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2418

East Asian (EAS)

AF:

0.00

AC:

AN:

4434

South Asian (SAS)

AF:

0.00

AC:

AN:

3088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

43658

Other (OTH)

AF:

0.00

AC:

AN:

1200

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

0.34

(source)

DANN

Benign

0.33

PhyloP100

-5.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over