Genetic Variant NM_016441.3:c.328G>A (chr2-36356620-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_016441.3(CRIM1):c.328G>A(p.Glu110Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,094 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E110Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CRIM1
NM_016441.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54

Publications

0 publications found

Variant links:

Genes affected

CRIM1 (HGNC:2359): (cysteine rich transmembrane BMP regulator 1) This gene encodes a transmembrane protein containing six cysteine-rich repeat domains and an insulin-like growth factor-binding domain. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins. [provided by RefSeq, Nov 2010]

CRIM1 Gene-Disease associations (from GenCC):

colobomatous macrophthalmia-microcornea syndrome
Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CRIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3055066).

BS2

High AC in GnomAdExome4 at 5 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3 link	c.328G>A	p.Glu110Lys	missense_variant	Exon 1 of 17	ENST00000280527.7	NP_057525.1	Q9NZV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRIM1	ENST00000280527.7 link	c.328G>A	p.Glu110Lys	missense_variant	Exon 1 of 17	1	NM_016441.3	ENSP00000280527.2	Q9NZV1
CRIM1	ENST00000426856.1 link	c.178G>A	p.Glu60Lys	missense_variant	Exon 1 of 4	3		ENSP00000407636.1	H7C2T6
CRIM1	ENST00000428774.1 link	c.148G>A	p.Glu50Lys	missense_variant	Exon 1 of 2	3		ENSP00000415706.1	H7C458

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000419

AC:

AN:

238814

AF XY:

0.00000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000344

AC:

AN:

1454094

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109534

Other (OTH)

AF:

0.00

AC:

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.039

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.84

T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.045

N;.

PhyloP100

5.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.26

Sift

Benign

0.58

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.69

P;.

Vest4

0.37

MutPred

0.53

Gain of methylation at E110 (P = 0.0101);.;

MVP

0.50

MPC

0.27

ClinPred

0.32

GERP RS

2.6

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.088

gMVP

0.63

Mutation Taster

=64/36

polymorphism

(source)

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

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NM_016441.3:c.328G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over