dbSNP rs146190210: CCDC74B:p.Arg311Pro (chr2-130139568-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001258307.2(CCDC74B):c.932G>C(p.Arg311Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000705 in 1,613,384 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R311C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00072 ( 2 hom. )

Consequence

CCDC74B
NM_001258307.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

CCDC74B (HGNC:25267): (coiled-coil domain containing 74B)

CCDC74B links:

MED15P9 (HGNC:):

MED15P9 links:

MED15P9 (HGNC:44130): (mediator complex subunit 15 pseudogene 9)

MED15P9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74B	NM_001258307.2 link	c.932G>C	p.Arg311Pro	missense_variant	Exon 8 of 8	ENST00000409943.8	NP_001245236.1	Q96LY2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74B	ENST00000409943.8 link	c.932G>C	p.Arg311Pro	missense_variant	Exon 8 of 8	1	NM_001258307.2	ENSP00000386294.3		Q96LY2-2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000364

AC:

AN:

250084

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000567

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.000717

AC:

1047

AN:

1461008

Hom.:

Cov.:

AF XY:

0.000637

AC XY:

463

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000731

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000850

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000597

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000626

Hom.:

Bravo

AF:

0.000495

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.63

MVP

0.83

MPC

0.71

ClinPred

0.13

GERP RS

3.3

Varity_R

0.67

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over