1-173912755-C-T

Variant summary

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

The NM_000488.4(SERPINC1):c.409-741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,066 control chromosomes in the GnomAD database, including 937 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 0.10 (937 hom., cov: 32)
• Consequence: SERPINC1 NM_000488.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

SERPINC1 (HGNC:775): (serpin family C member 1) The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]

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 (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINC1	NM_000488.4	c.409-741G>A		intron_variant		ENST00000367698.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINC1	ENST00000367698.4	c.409-741G>A		intron_variant		1	NM_000488.4	P1
SERPINC1	ENST00000487183.1	n.114-741G>A		intron_variant, non_coding_transcript_variant		2
SERPINC1	ENST00000494024.1	n.635-741G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15165 AN: 151948 Hom.: 937 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0998 AC: 15172 AN: 152066 Hom.: 937 Cov.: 32 AF XY: 0.102 AC XY: 7569 AN XY: 74332

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0948 Hom.: 157

Bravo AF: 0.0966

Asia WGS AF: 0.220 AC: 764 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	1.9
Dann	Benign	0.41

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: rs941988; hg19: chr1-173881893;