Variant chr15-65385121-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020962.3(IGDCC4):c.3181-6G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,580,530 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 21 hom. )

Consequence

IGDCC4
NM_020962.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001239

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.335

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 15-65385121-C-G is Benign according to our data. Variant chr15-65385121-C-G is described in ClinVar as [Benign]. Clinvar id is 712622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00222 (338/151962) while in subpopulation AMR AF= 0.0195 (298/15276). AF 95% confidence interval is 0.0177. There are 7 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGDCC4	NM_020962.3 linkuse as main transcript	c.3181-6G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000352385.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
IGDCC4	ENST00000352385.3 linkuse as main transcript	c.3181-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_020962.3	P1	Q8TDY8-1
IGDCC4	ENST00000559327.1 linkuse as main transcript	n.2450-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
IGDCC4	ENST00000558048.5 linkuse as main transcript	n.313-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
IGDCC4	ENST00000561309.1 linkuse as main transcript	n.202-6G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

338

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000969

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00545

AC:

1063

AN:

195060

Hom.:

AF XY:

0.00412

AC XY:

451

AN XY:

109432

show subpopulations

Gnomad AFR exome

AF:

0.000526

Gnomad AMR exome

AF:

0.0348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000792

Gnomad SAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000230

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00104

AC:

1481

AN:

1428568

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

672

AN XY:

710724

show subpopulations

Gnomad4 AFR exome

AF:

0.000311

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00288

Gnomad4 SAS exome

AF:

0.000981

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.000942

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

151962

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

196

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000795

Hom.:

Bravo

AF:

0.00321

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.85

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0040

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