11-75571007-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINH1	NM_001235.5	c.955-774T>G		intron_variant		ENST00000358171.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINH1	ENST00000358171.8	c.955-774T>G		intron_variant		1	NM_001235.5	P1

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

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.797

Alfa AF: 0.841 Hom.: 67850

Bravo AF: 0.758

Asia WGS AF: 0.710 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.045
Dann	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs634552; hg19: chr11-75282052;