chr7-100685638-C-T

Variant names:

• chr7-100685638-C-T
• rs221795
• NM_001375765.1:c.1055-157G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375765.1(GIGYF1):​c.1055-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,110 control chromosomes in the GnomAD database, including 34,188 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 0.67 (34188 hom., cov: 33)
• Consequence: GIGYF1 NM_001375765.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 11 publications found

Genes affected

GIGYF1 (HGNC:9126): (GRB10 interacting GYF protein 1) This gene encodes a member of the gyf family of adaptor proteins. The encoded protein contains a gyf protein interaction domain. It binds growth factor receptor bound 10, another adaptor protein that binds activated insulin-like growth factor 1 and insulin receptors and regulates receptor signaling. [provided by RefSeq, Apr 2017]

GIGYF1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1	c.1055-157G>A		intron_variant	Intron 12 of 26	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF1	ENST00000678049.1	c.1055-157G>A		intron_variant	Intron 12 of 26		NM_001375765.1	ENSP00000503354.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101494 AN: 151992 Hom.: 34173 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.668 AC: 101551 AN: 152110 Hom.: 34188 Cov.: 33 AF XY: 0.672 AC XY: 49966 AN XY: 74354

African (AFR) AF: 0.664 AC: 27539 AN: 41488

American (AMR) AF: 0.753 AC: 11512 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2675 AN: 3468

East Asian (EAS) AF: 0.812 AC: 4197 AN: 5170

South Asian (SAS) AF: 0.730 AC: 3524 AN: 4830

European-Finnish (FIN) AF: 0.563 AC: 5953 AN: 10580

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43855 AN: 67974

Other (OTH) AF: 0.730 AC: 1542 AN: 2112

Alfa AF: 0.668 Hom.: 59525

Bravo AF: 0.680

Asia WGS AF: 0.739 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.79
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs221795; hg19: chr7-100283261;