2-131528195-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001258306.3(CCDC74A):​c.225C>T​(p.Ile75Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CCDC74A
NM_001258306.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.195
Variant links:
Genes affected
CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
Synonymous conserved (PhyloP=0.195 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC74ANM_001258306.3 linkc.225C>T p.Ile75Ile synonymous_variant Exon 1 of 8 ENST00000409856.8 NP_001245235.1 Q96AQ1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC74AENST00000409856.8 linkc.225C>T p.Ile75Ile synonymous_variant Exon 1 of 8 1 NM_001258306.3 ENSP00000387009.3 Q96AQ1-2

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152132
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000487
AC:
12
AN:
246552
Hom.:
0
AF XY:
0.0000672
AC XY:
9
AN XY:
133946
show subpopulations
Gnomad AFR exome
AF:
0.000251
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000364
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.0000329
AC:
48
AN:
1461132
Hom.:
0
Cov.:
32
AF XY:
0.0000440
AC XY:
32
AN XY:
726844
show subpopulations
Gnomad4 AFR exome
AF:
0.000747
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152248
Hom.:
0
Cov.:
31
AF XY:
0.000107
AC XY:
8
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.000385
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
11
DANN
Benign
0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142090969; hg19: chr2-132285768; API