chr2-187554751-G-A

Variant names:

• chr2-187554751-G-A
• rs10931292
• ENST00000729959.1:n.345G>A

Variant summary

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

The ENST00000729959.1(CALCRL-AS1):​n.345G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,186 control chromosomes in the GnomAD database, including 58,976 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 0.88 (58976 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CALCRL-AS1 ENST00000729959.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 9 publications found

Genes affected

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

TFPI (HGNC:11760): (tissue factor pathway inhibitor) This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL-AS1	ENST00000729959.1	n.345G>A		non_coding_transcript_exon_variant	Exon 3 of 3
CALCRL-AS1	ENST00000729960.1	n.347G>A		non_coding_transcript_exon_variant	Exon 3 of 3
TFPI	ENST00000421427.5	c.-274-402C>T		intron_variant	Intron 1 of 4	3		ENSP00000408170.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133583 AN: 152066 Hom.: 58930 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.878 AC: 133687 AN: 152186 Hom.: 58976 Cov.: 32 AF XY: 0.874 AC XY: 64978 AN XY: 74386

African (AFR) AF: 0.936 AC: 38861 AN: 41540

American (AMR) AF: 0.898 AC: 13721 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3472

East Asian (EAS) AF: 0.687 AC: 3545 AN: 5162

South Asian (SAS) AF: 0.890 AC: 4297 AN: 4830

European-Finnish (FIN) AF: 0.742 AC: 7851 AN: 10574

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59108 AN: 68000

Other (OTH) AF: 0.896 AC: 1894 AN: 2114

Alfa AF: 0.897 Hom.: 14068

Bravo AF: 0.893

Asia WGS AF: 0.823 AC: 2865 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	3.0
DANN	Benign	0.45
PhyloP100		0.50
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10931292; hg19: chr2-188419478;