Variant 6-151585974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_025059.4(CCDC170):c.1178G>A(p.Arg393Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,614,100 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 11 hom. )

Consequence

CCDC170
NM_025059.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.67

Variant links:

Genes affected

CCDC170 (HGNC:21177): (coiled-coil domain containing 170) The function of this gene and its encoded protein is not known. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and bone mineral density, but no link to this specific gene has been found. [provided by RefSeq, May 2010]

CCDC170 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005603671).

BP6

Variant 6-151585974-G-A is Benign according to our data. Variant chr6-151585974-G-A is described in ClinVar as [Benign]. Clinvar id is 710997.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00734 (1118/152324) while in subpopulation AFR AF= 0.0257 (1068/41570). AF 95% confidence interval is 0.0244. There are 10 homozygotes in gnomad4. There are 507 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC170	NM_025059.4 linkuse as main transcript	c.1178G>A	p.Arg393Lys	missense_variant	7/11	ENST00000239374.8
CCDC170	XM_011536147.3 linkuse as main transcript	c.1196G>A	p.Arg399Lys	missense_variant	7/11
CCDC170	XM_011536148.3 linkuse as main transcript	c.1111-7133G>A		intron_variant
CCDC170	XM_047419372.1 linkuse as main transcript	c.1093-7133G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8 linkuse as main transcript	c.1178G>A	p.Arg393Lys	missense_variant	7/11	1	NM_025059.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00735

AC:

1119

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00185

AC:

461

AN:

248938

Hom.:

AF XY:

0.00143

AC XY:

193

AN XY:

135048

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000707

AC:

1034

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

475

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00734

AC:

1118

AN:

152324

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00824

ESP6500AA

AF:

0.0253

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00223

AC:

269

Asia WGS

AF:

0.000866

AC:

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

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Benign

0.55

Polyphen

1.0

Vest4

0.17

MVP

0.34

MPC

0.40

ClinPred

0.031

GERP RS

5.8

Varity_R

0.56

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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