rs2483704

Positions:

• chr1-66729670-G-A
• chr1-66729670-G-C

Variant summary

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

The NM_032291.4(SGIP1):​c.1898+251G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,006 control chromosomes in the GnomAD database, including 11,527 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 0.38 (11527 hom., cov: 32)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGIP1	NM_032291.4	c.1898+251G>A		intron_variant		ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9	c.1898+251G>A		intron_variant		1	NM_032291.4	ENSP00000360076

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57237 AN: 151886 Hom.: 11525 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.377 AC: 57261 AN: 152006 Hom.: 11527 Cov.: 32 AF XY: 0.372 AC XY: 27671 AN XY: 74290

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.375

Alfa AF: 0.395 Hom.: 15618

Bravo AF: 0.367

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
DANN	Benign	0.68

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: rs2483704; hg19: chr1-67195353; COSMIC: COSV52765121;