Genetic Variant C1QTNF1:p.Tyr145Tyr (chr17-79047677-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_030968.5(C1QTNF1):c.435C>T(p.Tyr145Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,613,954 control chromosomes in the GnomAD database, including 386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 208 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 178 hom. )

Consequence

C1QTNF1
NM_030968.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.362

Variant links:

Genes affected

C1QTNF1 (HGNC:14324): (C1q and TNF related 1) Enables collagen binding activity. Involved in several processes, including negative regulation of platelet aggregation; positive regulation of aldosterone secretion; and positive regulation of cytosolic calcium ion concentration. Located in extracellular space. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-79047677-C-T is Benign according to our data. Variant chr17-79047677-C-T is described in ClinVar as [Benign]. Clinvar id is 781391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.362 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF1	NM_030968.5 link	c.435C>T	p.Tyr145Tyr	synonymous_variant	Exon 4 of 4	ENST00000579760.6	NP_112230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF1	ENST00000579760.6 link	c.435C>T	p.Tyr145Tyr	synonymous_variant	Exon 4 of 4	1	NM_030968.5	ENSP00000463922.1		Q9BXJ1-1

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4133

AN:

152144

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0947

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00711

AC:

1787

AN:

251176

Hom.:

AF XY:

0.00510

AC XY:

692

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0961

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00285

AC:

4162

AN:

1461692

Hom.:

178

Cov.:

AF XY:

0.00252

AC XY:

1830

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0977

Gnomad4 AMR exome

AF:

0.00541

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.00619

GnomAD4 genome

AF:

0.0272

AC:

4149

AN:

152262

Hom.:

208

Cov.:

AF XY:

0.0259

AC XY:

1926

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0948

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0313

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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