dbSNP rs35223184: IGDCC4:p.Asp243Asn (chr15-65400920-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_020962.3(IGDCC4):c.727G>A(p.Asp243Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00976 in 1,614,186 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0071 ( 3 hom., cov: 32)

Exomes 𝑓: 0.010 ( 84 hom. )

Consequence

IGDCC4
NM_020962.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

11 publications found

Variant links:

Genes affected

IGDCC4 (HGNC:13770): (immunoglobulin superfamily DCC subclass member 4) Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGDCC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.00790751).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020962.3. 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
	IGDCC4	NM_020962.3	MANE Select	c.727G>A	p.Asp243Asn	missense	Exon 5 of 20	NP_066013.1	Q8TDY8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGDCC4	ENST00000352385.3	TSL:1 MANE Select	c.727G>A	p.Asp243Asn	missense	Exon 5 of 20	ENSP00000319623.3	Q8TDY8-1
IGDCC4	ENST00000961839.1		c.727G>A	p.Asp243Asn	missense	Exon 5 of 20	ENSP00000631898.1
IGDCC4	ENST00000860245.1		c.727G>A	p.Asp243Asn	missense	Exon 5 of 20	ENSP00000530304.1

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1076

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00892

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00820

AC:

2061

AN:

251340

AF XY:

0.00855

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00442

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.0100

AC:

14676

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

7187

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00194

AC:

AN:

33480

American (AMR)

AF:

0.00452

AC:

202

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00861

AC:

225

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00922

AC:

795

AN:

86258

European-Finnish (FIN)

AF:

0.0132

AC:

703

AN:

53402

Middle Eastern (MID)

AF:

0.00729

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0109

AC:

12101

AN:

1112006

Other (OTH)

AF:

0.00897

AC:

542

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

852

1704

2555

3407

4259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.00706

AC:

1075

AN:

152324

Hom.:

Cov.:

AF XY:

0.00749

AC XY:

558

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41576

American (AMR)

AF:

0.00614

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00872

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0128

AC:

136

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

700

AN:

68030

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00898

Hom.:

Bravo

AF:

0.00633

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00896

AC:

ExAC

AF:

0.00818

AC:

993

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00812

EpiControl

AF:

0.00836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

PhyloP100

2.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

REVEL

Benign

0.17

Sift

Benign

0.074

Sift4G

Uncertain

0.029

Polyphen

0.32

Vest4

0.34

MVP

0.61

MPC

0.14

ClinPred

0.029

GERP RS

5.2

Varity_R

0.29

gMVP

0.44

Mutation Taster

=94/6

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