NM_001258307.2:c.580A>G

Variant names:

• chr2-130140277-T-C
• rs142933831
• NM_001258307.2:c.580A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001258307.2(CCDC74B):​c.580A>G​(p.Met194Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053344637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	NM_001258307.2	MANE Select	c.580A>G	p.Met194Val	missense	Exon 5 of 8	NP_001245236.1	Q96LY2-2
	CCDC74B	NM_207310.4		c.778A>G	p.Met260Val	missense	Exon 5 of 8	NP_997193.1	Q96LY2-1
	CCDC74B	NR_165309.1		n.863A>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	ENST00000409943.8	TSL:1 MANE Select	c.580A>G	p.Met194Val	missense	Exon 5 of 8	ENSP00000386294.3	Q96LY2-2
	CCDC74B	ENST00000860854.1		c.790A>G	p.Met264Val	missense	Exon 5 of 8	ENSP00000530913.1
	CCDC74B	ENST00000944366.1		c.790A>G	p.Met264Val	missense	Exon 5 of 8	ENSP00000614425.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 249680 AF XY: 0.000126

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.000276

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000142 AC: 207 AN: 1461022 Hom.: 1 Cov.: 34 AF XY: 0.000143 AC XY: 104 AN XY: 726802

African (AFR) AF: 0.000120 AC: 4 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.000167 AC: 186 AN: 1111644

Other (OTH) AF: 0.000116 AC: 7 AN: 60350

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152112 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.16
DANN	Benign	0.35
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.015
Sift	Benign	0.67	T
Sift4G	Benign	0.067	T
Polyphen		0.0010	B
Vest4		0.19
MVP		0.12
MPC		1.4
ClinPred		0.041	T
GERP RS		-4.3
Varity_R		0.14
gMVP		0.071
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs142933831; hg19: chr2-130897850;