rs3128396

Positions:

• chr7-112430182-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000005558.8(IFRD1):​c.-182+6750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 152,324 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0070 (10 hom., cov: 32)
• Consequence: IFRD1 ENST00000005558.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

LOC105375457 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1064/152324) while in subpopulation AFR AF= 0.0245 (1018/41554). AF 95% confidence interval is 0.0232. There are 10 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105375457	XR_001745325.2	n.3832C>T		non_coding_transcript_exon_variant	3/3
IFRD1	NM_001007245.3	c.-182+6750G>A		intron_variant
IFRD1	NM_001197080.2	c.-57+6750G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000005558.8	c.-182+6750G>A		intron_variant		1		P3
IFRD1	ENST00000432734.1	c.-182+6750G>A		intron_variant		4
IFRD1	ENST00000621379.4	c.-57+6750G>A		intron_variant		2		A1
IFRD1	ENST00000675578.1	c.-112+6750G>A		intron_variant				P3

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1065 AN: 152206 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00699 AC: 1064 AN: 152324 Hom.: 10 Cov.: 32 AF XY: 0.00694 AC XY: 517 AN XY: 74488

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00513 Hom.: 0

Bravo AF: 0.00817

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs3128396; hg19: chr7-112070237;