rs2146904

chr1-66694653-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.1571-781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 491,568 control chromosomes in the GnomAD database, including 96,840 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 0.63 (30512 hom., cov: 31)
  • Exomes 𝑓: 0.61 (66328 hom.)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGIP1	NM_032291.4	c.1571-781A>G		intron_variant		ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9	c.1571-781A>G		intron_variant		1	NM_032291.4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94997 AN: 151872 Hom.: 30472 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.612 AC: 207846 AN: 339578 Hom.: 66328 Cov.: 6 AF XY: 0.612 AC XY: 104691 AN XY: 171060

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.626 AC: 95095 AN: 151990 Hom.: 30512 Cov.: 31 AF XY: 0.628 AC XY: 46654 AN XY: 74282

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.620

Alfa AF: 0.602 Hom.: 13988

Bravo AF: 0.638

Asia WGS AF: 0.876 AC: 3047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.020
Dann	Benign	0.45

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: rs2146904; hg19: chr1-67160336;