rs1457118986

Variant names:

• chr2-131528026-G-A
• rs1457118986
• NM_001258306.3:c.56G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-131528026-G-A
• chr2-131528026-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001258306.3(CCDC74A):​c.56G>A​(p.Gly19Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000469 in 1,491,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20575681).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258306.3. 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
	CCDC74A	NM_001258306.3	MANE Select	c.56G>A	p.Gly19Asp	missense	Exon 1 of 8	NP_001245235.1	Q96AQ1-2
	CCDC74A	NM_001349042.2		c.56G>A	p.Gly19Asp	missense	Exon 1 of 8	NP_001335971.1
	CCDC74A	NM_138770.4		c.56G>A	p.Gly19Asp	missense	Exon 1 of 8	NP_620125.1	Q96AQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74A	ENST00000409856.8	TSL:1 MANE Select	c.56G>A	p.Gly19Asp	missense	Exon 1 of 8	ENSP00000387009.3	Q96AQ1-2
	CCDC74A	ENST00000295171.10	TSL:1	c.56G>A	p.Gly19Asp	missense	Exon 1 of 8	ENSP00000295171.6	Q96AQ1-1
	CCDC74A	ENST00000467992.6	TSL:1	c.56G>A	p.Gly19Asp	missense	Exon 1 of 7	ENSP00000444610.2	F5GZA4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151898 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000972 AC: 1 AN: 102848 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000448 AC: 6 AN: 1339230 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 655646

African (AFR) AF: 0.00 AC: 0 AN: 29560

American (AMR) AF: 0.0000432 AC: 1 AN: 23122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20550

East Asian (EAS) AF: 0.00 AC: 0 AN: 36336

South Asian (SAS) AF: 0.00 AC: 0 AN: 68934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3798

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1055874

Other (OTH) AF: 0.00 AC: 0 AN: 55058

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151898 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74184

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.070
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.033	D
Polyphen		0.55	P
Vest4		0.15
MutPred		0.20		Gain of helix (P = 0.0325)
MVP		0.20
MPC		2.2
ClinPred		0.37	T
GERP RS		1.2
PromoterAI		0.0054	Neutral
Varity_R		0.17
gMVP		0.094
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1457118986; hg19: chr2-132285599;