rs646474

Positions:

• chr11-75568402-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001235.5(SERPINH1):​c.623-329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 410,126 control chromosomes in the GnomAD database, including 45,139 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 0.40 (14298 hom., cov: 31)
  • Exomes 𝑓: 0.47 (30841 hom.)
• Consequence: SERPINH1 NM_001235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINH1	NM_001235.5	c.623-329T>C		intron_variant		ENST00000358171.8	NP_001226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINH1	ENST00000358171.8	c.623-329T>C		intron_variant		1	NM_001235.5	ENSP00000350894.4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60609 AN: 151926 Hom.: 14299 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.473 AC: 121992 AN: 258082 Hom.: 30841 Cov.: 0 AF XY: 0.462 AC XY: 63919 AN XY: 138220

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.399 AC: 60598 AN: 152044 Hom.: 14298 Cov.: 31 AF XY: 0.391 AC XY: 29038 AN XY: 74312

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.452

Alfa AF: 0.479 Hom.: 9073

Bravo AF: 0.386

Asia WGS AF: 0.271 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.74

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: rs646474; hg19: chr11-75279447;