rs199624326

Variant names:

• chr7-100685330-T-A
• rs199624326
• NM_001375765.1:c.1192+14A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 VariationId is 445298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 474 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375765.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	NM_001375765.1	MANE Select	c.1192+14A>T		intron	N/A	NP_001362694.1
	GIGYF1	NM_001375759.1		c.1192+14A>T		intron	N/A	NP_001362688.1
	GIGYF1	NM_001375760.1		c.1192+14A>T		intron	N/A	NP_001362689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	ENST00000678049.1	MANE Select	c.1192+14A>T		intron	N/A	ENSP00000503354.1
	GIGYF1	ENST00000275732.5	TSL:1	c.1192+14A>T		intron	N/A	ENSP00000275732.4
	GIGYF1	ENST00000646601.1		c.1192+14A>T		intron	N/A	ENSP00000494292.1

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

GnomAD2 exomes AF: 0.00362 AC: 822 AN: 226902 AF XY: 0.00357

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 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

African (AFR) AF: 0.000158 AC: 5 AN: 31586

American (AMR) AF: 0.00100 AC: 37 AN: 36858

Ashkenazi Jewish (ASJ) AF: 0.0000404 AC: 1 AN: 24722

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.0000607 AC: 5 AN: 82316

European-Finnish (FIN) AF: 0.0166 AC: 879 AN: 52972

Middle Eastern (MID) AF: 0.000209 AC: 1 AN: 4780

European-Non Finnish (NFE) AF: 0.00354 AC: 3894 AN: 1100582

Other (OTH) AF: 0.00241 AC: 142 AN: 58862

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

African (AFR) AF: 0.000554 AC: 23 AN: 41552

American (AMR) AF: 0.000523 AC: 8 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00347 AC: 236 AN: 68000

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00273 Hom.: 0

Bravo AF: 0.00173

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.78
DANN	Benign	0.58
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

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: rs199624326; hg19: chr7-100282953;