Genetic Variant HRNR:p.Tyr2707Tyr (chr1-152213508-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.8121C>T(p.Tyr2707Tyr) 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: 8.0e-7 ( 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: -0.349

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=-0.99).

BP6

Variant 1-152213508-G-A is Benign according to our data. Variant chr1-152213508-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3388751.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.349 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.8121C>T	p.Tyr2707Tyr	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
CCDST	NR_186761.1		n.353+23853G>A		intron	N/A
CCDST	NR_186762.1		n.179+24027G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRNR	ENST00000368801.4	TSL:1 MANE Select	c.8121C>T	p.Tyr2707Tyr	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
CCDST	ENST00000420707.5	TSL:5	n.158+24000G>A		intron	N/A
CCDST	ENST00000593011.5	TSL:4	n.296+45088G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

100824

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:

0.0000135

AC:

AN:

148666

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000178

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.95e-7

AC:

AN:

1257734

Hom.:

Cov.:

AF XY:

0.00000159

AC XY:

AN XY:

630728

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

29764

American (AMR)

AF:

0.00

AC:

AN:

42442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23374

East Asian (EAS)

AF:

0.00

AC:

AN:

39288

South Asian (SAS)

AF:

0.00

AC:

AN:

82926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4346

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

932462

Other (OTH)

AF:

0.00

AC:

AN:

53702

⚠️ 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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

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

AF:

0.00

AC:

AN:

100824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

47812

African (AFR)

AF:

0.00

AC:

AN:

27504

American (AMR)

AF:

0.00

AC:

AN:

9394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2430

East Asian (EAS)

AF:

0.00

AC:

AN:

4412

South Asian (SAS)

AF:

0.00

AC:

AN:

3142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

45890

Other (OTH)

AF:

0.00

AC:

AN:

1240

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

-0.99

CADD

Benign

0.15

(source)

DANN

Benign

0.33

PhyloP100

-0.35

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over