chr17-4988916-C-T

Variant names:

• chr17-4988916-C-T
• NM_001394789.1:c.424G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394789.1(INCA1):​c.424G>A​(p.Gly142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: INCA1 NM_001394789.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.731
• Publications: 0 publications found

Genes affected

INCA1 (HGNC:32224): (inhibitor of CDK, cyclin A1 interacting protein 1) Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

CAMTA2-AS1 (HGNC:55342): (CAMTA2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058867157).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394789.1. 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
	INCA1	NM_001394789.1	MANE Select	c.424G>A	p.Gly142Arg	missense	Exon 6 of 7	NP_001381718.1	Q0VD86-1
	INCA1	NM_001167986.2		c.424G>A	p.Gly142Arg	missense	Exon 8 of 9	NP_001161458.1	Q0VD86-1
	INCA1	NM_001167987.2		c.424G>A	p.Gly142Arg	missense	Exon 7 of 8	NP_001161459.1	Q0VD86-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INCA1	ENST00000695324.1	MANE Select	c.424G>A	p.Gly142Arg	missense	Exon 6 of 7	ENSP00000511805.1	Q0VD86-1
	INCA1	ENST00000574617.1	TSL:1	c.424G>A	p.Gly142Arg	missense	Exon 7 of 8	ENSP00000458316.1	Q0VD86-1
	INCA1	ENST00000576820.5	TSL:1	c.424G>A	p.Gly142Arg	missense	Exon 6 of 7	ENSP00000460673.1	Q0VD86-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

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	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.73
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.061
Sift	Benign	0.038	D
Sift4G	Benign	0.068	T
Polyphen		0.0040	B
Vest4		0.18
MutPred		0.20		Gain of MoRF binding (P = 0.0089)
MVP		0.12
ClinPred		0.11	T
GERP RS		-2.0
Varity_R		0.27
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr17-4892211;