7-100682316-G-C

Variant names:

• chr7-100682316-G-C
• rs200383064
• NM_001375765.1:c.2761+6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001375765.1(GIGYF1):​c.2761+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GIGYF1 NM_001375765.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002407
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	NM_001375765.1	MANE Select	c.2761+6C>G		splice_region intron	N/A	NP_001362694.1	O75420
	GIGYF1	NM_001375759.1		c.2761+6C>G		splice_region intron	N/A	NP_001362688.1
	GIGYF1	NM_001375760.1		c.2761+6C>G		splice_region intron	N/A	NP_001362689.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	ENST00000678049.1	MANE Select	c.2761+6C>G		splice_region intron	N/A	ENSP00000503354.1	O75420
	GIGYF1	ENST00000275732.5	TSL:1	c.2761+6C>G		splice_region intron	N/A	ENSP00000275732.4	O75420
	GIGYF1	ENST00000893817.1		c.2794+6C>G		splice_region intron	N/A	ENSP00000563876.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458622 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725634

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111366

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.39
SpliceAI score (max)		0.060		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: rs200383064; hg19: chr7-100279939;