Variant 16-1614673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020825.4(CRAMP1):c.34G>A(p.Glu12Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000115 in 1,303,958 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: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CRAMP1
NM_020825.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16622716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAMP1	NM_020825.4 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	2/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CRAMP1	ENST00000397412.8 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	2/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/20	5		P1
CRAMP1	ENST00000674071.1 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.0000628

AC:

AN:

47770

Hom.:

AF XY:

0.0000700

AC XY:

AN XY:

28572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000792

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000113

AC:

AN:

1152690

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

557628

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000650

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:

0.00000210

Gnomad4 OTH exome

AF:

0.0000659

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73852

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

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

Bravo

AF:

0.0000567

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

Jan 18, 2023

The c.34G>A (p.E12K) alteration is located in exon 1 (coding exon 1) of the CRAMP1 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the glutamic acid (E) at amino acid position 12 to be replaced by a lysine (K). 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

0.31

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.47

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

0.072

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.62

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.27

T;T

Polyphen

0.98

D;D

Vest4

0.21

MutPred

0.19

Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);

MVP

0.043

MPC

1.4

ClinPred

0.24

GERP RS

1.9

Varity_R

0.24

gMVP

0.23

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