Variant 16-1614944-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020825.4(CRAMP1):c.305T>C(p.Val102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,269,738 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: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

CRAMP1
NM_020825.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058465064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAMP1	NM_020825.4 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	2/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRAMP1	ENST00000397412.8 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	2/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9 linkuse as main transcript	c.305T>C	p.Val102Ala	missense_variant	1/20	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

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:

0.000956

GnomAD4 exome

AF:

0.00000984

AC:

AN:

1117530

Hom.:

Cov.:

AF XY:

0.00000747

AC XY:

AN XY:

535550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.000184

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00150

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:

0.000946

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000533

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

Oct 30, 2023

The c.305T>C (p.V102A) alteration is located in exon 1 (coding exon 1) of the CRAMP1 gene. This alteration results from a T to C substitution at nucleotide position 305, causing the valine (V) at amino acid position 102 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

Cadd

Benign

7.4

Dann

Benign

0.47

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

M_CAP

Benign

0.0057

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.021

Sift

Benign

0.21

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.037

MutPred

0.15

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.13

MPC

1.2

ClinPred

0.11

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.079

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

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