rs199624326

Positions:

• chr7-100685330-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001375765.1(GIGYF1):​c.1192+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,584,222 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (10 hom.)
• Consequence: GIGYF1 NM_001375765.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-100685330-T-A is Benign according to our data. Variant chr7-100685330-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 445298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF1	NM_001375765.1	c.1192+14A>T		intron_variant		ENST00000678049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF1	ENST00000678049.1	c.1192+14A>T		intron_variant			NM_001375765.1	P1
GIGYF1	ENST00000275732.5	c.1192+14A>T		intron_variant		1		P1
GIGYF1	ENST00000646601.1	c.1192+14A>T		intron_variant				P1
GIGYF1	ENST00000471340.2	n.422-436A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00312 AC: 474 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00362 AC: 822 AN: 226902 Hom.: 2 AF XY: 0.00357 AC XY: 441 AN XY: 123424

Gnomad AFR exome AF: 0.000317

Gnomad AMR exome AF: 0.000903

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.00370

Gnomad OTH exome AF: 0.00274

GnomAD4 exome AF: 0.00347 AC: 4964 AN: 1431950 Hom.: 10 Cov.: 33 AF XY: 0.00338 AC XY: 2407 AN XY: 711372

Gnomad4 AFR exome AF: 0.000158

Gnomad4 AMR exome AF: 0.00100

Gnomad4 ASJ exome AF: 0.0000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000607

Gnomad4 FIN exome AF: 0.0166

Gnomad4 NFE exome AF: 0.00354

Gnomad4 OTH exome AF: 0.00241

GnomAD4 genome AF: 0.00311 AC: 474 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00363 AC XY: 270 AN XY: 74460

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00273 Hom.: 0

Bravo AF: 0.00173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.78
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs199624326; hg19: chr7-100282953;