1-152215572-A-G

Variant names:

• chr1-152215572-A-G
• rs578136582
• NM_001009931.3:c.6057T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001009931.3(HRNR):​c.6057T>C​(p.His2019His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 125,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000088 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-152215572-A-G is Benign according to our data. Variant chr1-152215572-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2639203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	NM_001009931.3	MANE Select	c.6057T>C	p.His2019His	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+25917A>G		intron	N/A
	CCDST	NR_186762.1		n.179+26091A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6057T>C	p.His2019His	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+26064A>G		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+47152A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000876 AC: 11 AN: 125564 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000958

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000609

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00424

Gnomad NFE AF: 0.0000835

Gnomad OTH AF: 0.000592

GnomAD2 exomes AF: 0.00000438 AC: 1 AN: 228266 AF XY: 0.00

Gnomad AFR exome AF: 0.0000631

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000301 AC: 406 AN: 1350720 Hom.: 0 Cov.: 224 AF XY: 0.000445 AC XY: 300 AN XY: 673770

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

African (AFR) AF: 0.0000310 AC: 1 AN: 32308

American (AMR) AF: 0.00 AC: 0 AN: 38596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24388

East Asian (EAS) AF: 0.000419 AC: 13 AN: 31004

South Asian (SAS) AF: 0.00458 AC: 352 AN: 76784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51348

Middle Eastern (MID) AF: 0.000776 AC: 4 AN: 5154

European-Non Finnish (NFE) AF: 0.0000164 AC: 17 AN: 1035848

Other (OTH) AF: 0.000344 AC: 19 AN: 55290

⚠️ 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.

GnomAD4 genome AF: 0.0000875 AC: 11 AN: 125650 Hom.: 0 Cov.: 33 AF XY: 0.000115 AC XY: 7 AN XY: 60782

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

African (AFR) AF: 0.0000290 AC: 1 AN: 34534

American (AMR) AF: 0.0000958 AC: 1 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2692

East Asian (EAS) AF: 0.00 AC: 0 AN: 2936

South Asian (SAS) AF: 0.000609 AC: 2 AN: 3286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9232

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.0000835 AC: 5 AN: 59862

Other (OTH) AF: 0.000585 AC: 1 AN: 1710

⚠️ 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.

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.19
DANN	Benign	0.61
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs578136582; hg19: chr1-152188048;