11-75566213-G-A

Position:

• chr11-75566213-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BS2_Supporting

The NM_001235.5(SERPINH1):​c.-34-103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,046,974 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (44 hom.)
• Consequence: SERPINH1 NM_001235.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.455

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-75566213-G-A is Benign according to our data. Variant chr11-75566213-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 676717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINH1	NM_001235.5	c.-34-103G>A		intron_variant		ENST00000358171.8	NP_001226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINH1	ENST00000358171.8	c.-34-103G>A		intron_variant		1	NM_001235.5	ENSP00000350894.4

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1010 AN: 152182 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00783 AC: 7008 AN: 894674 Hom.: 44 AF XY: 0.00769 AC XY: 3518 AN XY: 457644

Gnomad4 AFR exome AF: 0.000972

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.00204

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00955

Gnomad4 OTH exome AF: 0.00717

GnomAD4 genome AF: 0.00663 AC: 1010 AN: 152300 Hom.: 3 Cov.: 33 AF XY: 0.00659 AC XY: 491 AN XY: 74470

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0143 Hom.: 4

Bravo AF: 0.00589

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.50

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: rs147548875; hg19: chr11-75277258;