Variant 5-177404979-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000505.4(F12):c.530-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 1,588,580 control chromosomes in the GnomAD database, including 759,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.97 ( 70972 hom., cov: 31)

Exomes 𝑓: 0.98 ( 688504 hom. )

Consequence

F12
NM_000505.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.85

Variant links:

Genes affected

F12 (HGNC:3530): (coagulation factor XII) This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged. [provided by RefSeq, Jul 2008]

F12 links:

GRK6 (HGNC:4545): (G protein-coupled receptor kinase 6) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

GRK6 links:

F12 (HGNC:):

F12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-177404979-T-C is Benign according to our data. Variant chr5-177404979-T-C is described in ClinVar as [Benign]. Clinvar id is 1249273.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F12	NM_000505.4 linkuse as main transcript	c.530-65A>G		intron_variant		ENST00000253496.4	NP_000496.2	P00748Q8IZZ5
F12	XM_011534462.3 linkuse as main transcript	c.194-65A>G		intron_variant			XP_011532764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F12	ENST00000253496.4 linkuse as main transcript	c.530-65A>G		intron_variant		1	NM_000505.4	ENSP00000253496.3		P00748

Frequencies

GnomAD3 genomes

AF:

0.965

AC:

146749

AN:

152034

Hom.:

70934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.960

Gnomad AMI

AF:

0.882

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.990

Gnomad EAS

AF:

0.899

Gnomad SAS

AF:

0.955

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.967

GnomAD4 exome

AF:

0.979

AC:

1405651

AN:

1436428

Hom.:

688504

Cov.:

AF XY:

0.979

AC XY:

698510

AN XY:

713848

show subpopulations

Gnomad4 AFR exome

AF:

0.956

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.987

Gnomad4 EAS exome

AF:

0.915

Gnomad4 SAS exome

AF:

0.958

Gnomad4 FIN exome

AF:

0.989

Gnomad4 NFE exome

AF:

0.988

Gnomad4 OTH exome

AF:

0.974

GnomAD4 genome

AF:

0.965

AC:

146841

AN:

152152

Hom.:

70972

Cov.:

AF XY:

0.963

AC XY:

71628

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.960

Gnomad4 AMR

AF:

0.886

Gnomad4 ASJ

AF:

0.990

Gnomad4 EAS

AF:

0.898

Gnomad4 SAS

AF:

0.955

Gnomad4 FIN

AF:

0.989

Gnomad4 NFE

AF:

0.988

Gnomad4 OTH

AF:

0.964

Alfa

AF:

0.975

Hom.:

9701

Bravo

AF:

0.956

Asia WGS

AF:

0.926

AC:

3223

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.23

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over