rs10190564

Variant names:

• chr2-131530663-C-G
• rs10190564
• ENST00000295171.10:c.380C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-131530663-C-G
• chr2-131530663-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349042.2(CCDC74A):​c.506C>G​(p.Pro169Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,611,848 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 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. P169L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.024 (61 hom., cov: 29)
  • Exomes 𝑓: 0.0024 (17 hom.)
• Consequence: CCDC74A NM_001349042.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.01

Genes affected

CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024795234).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74A	NM_001258306.3	c.296-114C>G		intron_variant	Intron 2 of 7	ENST00000409856.8	NP_001245235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74A	ENST00000409856.8	c.296-114C>G		intron_variant	Intron 2 of 7	1	NM_001258306.3	ENSP00000387009.3

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3546 AN: 151320 Hom.: 58 Cov.: 29

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00789

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00355

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.00554 AC: 1369 AN: 246978 Hom.: 1 AF XY: 0.00404 AC XY: 543 AN XY: 134378

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.00311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00239

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00236 AC: 3445 AN: 1460412 Hom.: 17 Cov.: 38 AF XY: 0.00211 AC XY: 1534 AN XY: 726546

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00556

GnomAD4 genome AF: 0.0235 AC: 3559 AN: 151436 Hom.: 61 Cov.: 29 AF XY: 0.0229 AC XY: 1697 AN XY: 74014

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.00788

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00355

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.00116 Hom.: 0

ExAC AF: 0.00781 AC: 948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.28
DANN	Benign	0.70
DEOGEN2	Benign	0.0028	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.30	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PROVEAN	Benign	-0.26	N;.
REVEL	Benign	0.013
Sift	Benign	0.092	T;.
Sift4G	Benign	0.52	T;T
Polyphen		0.0080	B;.
Vest4		0.051
MVP		0.040
MPC		1.3
ClinPred		0.0037	T
GERP RS		-3.0
Varity_R		0.045
gMVP		0.081

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

Other links and lift over

dbSNP: rs10190564; hg19: chr2-132288236;