11-75571007-T-G

Variant names:

• chr11-75571007-T-G
• rs634552
• NM_001235.5:c.955-774T>G

Variant summary

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

The NM_001235.5(SERPINH1):​c.955-774T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,088 control chromosomes in the GnomAD database, including 46,426 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 0.77 (46426 hom., cov: 31)
• Consequence: SERPINH1 NM_001235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINH1	NM_001235.5	MANE Select	c.955-774T>G		intron	N/A	NP_001226.2
	SERPINH1	NM_001207014.3		c.955-774T>G		intron	N/A	NP_001193943.1
	SERPINH1	NM_001440311.1		c.955-774T>G		intron	N/A	NP_001427240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINH1	ENST00000358171.8	TSL:1 MANE Select	c.955-774T>G		intron	N/A	ENSP00000350894.4
	SERPINH1	ENST00000524558.5	TSL:2	c.955-774T>G		intron	N/A	ENSP00000434412.1
	SERPINH1	ENST00000533603.5	TSL:2	c.955-774T>G		intron	N/A	ENSP00000434657.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117728 AN: 151970 Hom.: 46390 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.775 AC: 117817 AN: 152088 Hom.: 46426 Cov.: 31 AF XY: 0.771 AC XY: 57349 AN XY: 74356

African (AFR) AF: 0.637 AC: 26381 AN: 41446

American (AMR) AF: 0.756 AC: 11558 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2780 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2830 AN: 5166

South Asian (SAS) AF: 0.862 AC: 4163 AN: 4830

European-Finnish (FIN) AF: 0.803 AC: 8497 AN: 10584

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

European-Non Finnish (NFE) AF: 0.867 AC: 58976 AN: 67992

Other (OTH) AF: 0.797 AC: 1680 AN: 2108

Alfa AF: 0.830 Hom.: 156596

Bravo AF: 0.758

Asia WGS AF: 0.710 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.39
PhyloP100		-2.0
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: rs634552; hg19: chr11-75282052;