Variant 16-1626057-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020825.4(CRAMP1):c.431G>A(p.Arg144Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000902 in 1,551,440 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

CRAMP1
NM_020825.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

CRAMP1 (HGNC:14122): (cramped chromatin regulator homolog 1) Predicted to enable chromatin binding activity. Predicted to be involved in pattern specification process. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CRAMP1 links:

ENSG00000226890 (HGNC:):

ENSG00000226890 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34723026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRAMP1	NM_020825.4 linkuse as main transcript	c.431G>A	p.Arg144Gln	missense_variant	3/21	ENST00000397412.8	NP_065876.3	Q96RY5B2RNX8A7MD53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRAMP1	ENST00000397412.8 linkuse as main transcript	c.431G>A	p.Arg144Gln	missense_variant	3/21	5	NM_020825.4	ENSP00000380559.2	Q96RY5
CRAMP1	ENST00000293925.9 linkuse as main transcript	c.431G>A	p.Arg144Gln	missense_variant	2/20	5		ENSP00000293925.5	Q96RY5
ENSG00000226890	ENST00000415176.1 linkuse as main transcript	n.104C>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1399236

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.431G>A (p.R144Q) alteration is located in exon 2 (coding exon 2) of the CRAMP1 gene. This alteration results from a G to A substitution at nucleotide position 431, causing the arginine (R) at amino acid position 144 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;D

Vest4

0.34

MutPred

0.16

Loss of MoRF binding (P = 0.0124);Loss of MoRF binding (P = 0.0124);

MVP

0.30

MPC

2.3

ClinPred

0.85

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.088

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over