Genetic Variant NM_001550.4:c.568-12T>A (chr7-112461854-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001550.4(IFRD1):c.568-12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,190,456 control chromosomes in the GnomAD database, including 246,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.73 ( 34129 hom., cov: 29)

Exomes 𝑓: 0.66 ( 212867 hom. )

Consequence

IFRD1
NM_001550.4 intron

Scores

Splicing: ADA: 0.00005965

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.424

Variant links:

Genes affected

IFRD1 (HGNC:5456): (interferon related developmental regulator 1) This gene is an immediate early gene that encodes a protein related to interferon-gamma. This protein may function as a transcriptional co-activator/repressor that controls the growth and differentiation of specific cell types during embryonic development and tissue regeneration. Mutations in this gene are associated with sensory/motor neuropathy with ataxia. This gene may also be involved in modulating the pathogenesis of cystic fibrosis lung disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

IFRD1 links:

ENSG00000288640 (HGNC:):

ENSG00000288640 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-112461854-T-A is Benign according to our data. Variant chr7-112461854-T-A is described in ClinVar as [Benign]. Clinvar id is 1284337.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-112461854-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4 link	c.568-12T>A		intron_variant	Intron 5 of 11	ENST00000403825.8	NP_001541.2	O00458-1A4D0U1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8 link	c.568-12T>A		intron_variant	Intron 5 of 11	1	NM_001550.4	ENSP00000384477.3		O00458-1
ENSG00000288640	ENST00000676282.1 link	n.568-12T>A		intron_variant	Intron 5 of 14			ENSP00000501830.1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

100257

AN:

138240

Hom.:

34113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.833

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.733

GnomAD3 exomes

AF:

0.589

AC:

110848

AN:

188114

Hom.:

29617

AF XY:

0.586

AC XY:

60049

AN XY:

102518

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.639

Gnomad NFE exome

AF:

0.670

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.661

AC:

695895

AN:

1052110

Hom.:

212867

Cov.:

AF XY:

0.658

AC XY:

348782

AN XY:

530212

show subpopulations

Gnomad4 AFR exome

AF:

0.697

Gnomad4 AMR exome

AF:

0.581

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.671

Gnomad4 NFE exome

AF:

0.691

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.725

AC:

100326

AN:

138346

Hom.:

34129

Cov.:

AF XY:

0.717

AC XY:

48196

AN XY:

67210

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.720

Gnomad4 NFE

AF:

0.751

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.687

Hom.:

3342

Bravo

AF:

0.662

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.014

SpliceAI score (max)

0.040

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