rs606452

Variant names:

• chr11-75565133-A-C
• rs606452
• NM_001235.5:c.-34-1183A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-75565133-A-C
• chr11-75565133-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001235.5(SERPINH1):​c.-34-1183A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,134 control chromosomes in the GnomAD database, including 46,576 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.

• Frequency: Genomes: 𝑓 0.78 (46576 hom., cov: 32)
• Consequence: SERPINH1 NM_001235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 47 publications found

Genes affected

SERPINH1 (HGNC:1546): (serpin family H member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The encoded protein is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Autoantibodies to the encoded protein have been found in patients with rheumatoid arthritis. Expression of this gene may be a marker for cancer, and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]

SERPINH1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 10

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINH1	NM_001235.5	c.-34-1183A>C		intron_variant	Intron 1 of 4	ENST00000358171.8	NP_001226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINH1	ENST00000358171.8	c.-34-1183A>C		intron_variant	Intron 1 of 4	1	NM_001235.5	ENSP00000350894.4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117931 AN: 152014 Hom.: 46536 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.776 AC: 118025 AN: 152134 Hom.: 46576 Cov.: 32 AF XY: 0.772 AC XY: 57412 AN XY: 74376

African (AFR) AF: 0.645 AC: 26748 AN: 41462

American (AMR) AF: 0.758 AC: 11600 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2764 AN: 3468

East Asian (EAS) AF: 0.516 AC: 2661 AN: 5154

South Asian (SAS) AF: 0.848 AC: 4091 AN: 4822

European-Finnish (FIN) AF: 0.802 AC: 8506 AN: 10602

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59011 AN: 68012

Other (OTH) AF: 0.800 AC: 1692 AN: 2114

Alfa AF: 0.834 Hom.: 221183

Bravo AF: 0.760

Asia WGS AF: 0.702 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

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: rs606452; hg19: chr11-75276178;