rs2146905

Positions:

• chr1-66701210-A-C
• chr1-66701210-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032291.4(SGIP1):​c.1630+5717A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,888 control chromosomes in the GnomAD database, including 14,293 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 0.42 (14293 hom., cov: 31)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

SGIP1 (HGNC:25412): (SH3GL interacting endocytic adaptor 1) SGIP1 functions as an endocytic protein that affects signaling by receptors in neuronal systems involved in energy homeostasis via its interaction with endophilins (see SH3GL3; MIM 603362) (Trevaskis et al., 2005 [PubMed 15919751] and Uezu et al., 2007 [PubMed 17626015]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGIP1	NM_032291.4	c.1630+5717A>C		intron_variant		ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9	c.1630+5717A>C		intron_variant		1	NM_032291.4

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64466 AN: 151770 Hom.: 14279 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.425 AC: 64516 AN: 151888 Hom.: 14293 Cov.: 31 AF XY: 0.426 AC XY: 31645 AN XY: 74240

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.450

Alfa AF: 0.425 Hom.: 6320

Bravo AF: 0.430

Asia WGS AF: 0.676 AC: 2352 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.73

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: rs2146905; hg19: chr1-67166893;