Genetic Variant HNRNPCL1:p.Glu250Asp (chr1-12847540-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013631.3(HNRNPCL1):c.750G>T(p.Glu250Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,606,718 control chromosomes in the GnomAD database, including 6 homozygotes. 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 0.00033 ( 2 hom., cov: 30)

Exomes 𝑓: 0.000051 ( 4 hom. )

Consequence

HNRNPCL1
NM_001013631.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

Genes affected

HNRNPCL1 (HGNC:29295): (heterogeneous nuclear ribonucleoprotein C like 1) Enables identical protein binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HNRNPCL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0141637325).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013631.3. 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
	HNRNPCL1	NM_001013631.3	MANE Select	c.750G>T	p.Glu250Asp	missense	Exon 2 of 2	NP_001013653.1	O60812

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPCL1	ENST00000317869.7	TSL:1 MANE Select	c.750G>T	p.Glu250Asp	missense	Exon 2 of 2	ENSP00000365370.4	O60812

Frequencies

GnomAD3 genomes

AF:

0.000313

AC:

AN:

149958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

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

GnomAD2 exomes

AF:

0.000116

AC:

AN:

250418

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.000177

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:

0.000163

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1456660

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724634

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

33386

American (AMR)

AF:

0.000184

AC:

AN:

43452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109112

Other (OTH)

AF:

0.000249

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000333

AC:

AN:

150058

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

AN XY:

73172

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

40970

American (AMR)

AF:

0.000138

AC:

AN:

14502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67574

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000385

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.2

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.28

M_CAP

Benign

0.0013

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

PhyloP100

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.097

Sift

Benign

0.13

Sift4G

Benign

0.10

Polyphen

0.39

Vest4

0.21

MutPred

0.10

Loss of helix (P = 0.1299)

MVP

0.20

MPC

0.059

ClinPred

0.038

GERP RS

-0.073

Varity_R

0.084

gMVP

0.033

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over