1-66580443-C-A

Variant names:

• chr1-66580443-C-A
• rs1867631
• NM_032291.4:c.11-45404C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032291.4(SGIP1):​c.11-45404C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,926 control chromosomes in the GnomAD database, including 11,433 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 0.37 (11433 hom., cov: 31)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGIP1	NM_032291.4	c.11-45404C>A		intron_variant	Intron 1 of 24	ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9	c.11-45404C>A		intron_variant	Intron 1 of 24	1	NM_032291.4	ENSP00000360076.3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56865 AN: 151806 Hom.: 11413 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.375 AC: 56930 AN: 151926 Hom.: 11433 Cov.: 31 AF XY: 0.372 AC XY: 27633 AN XY: 74242

African (AFR) AF: 0.517 AC: 21410 AN: 41408

American (AMR) AF: 0.428 AC: 6527 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 942 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2058 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4830

European-Finnish (FIN) AF: 0.246 AC: 2597 AN: 10556

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20990 AN: 67936

Other (OTH) AF: 0.359 AC: 757 AN: 2110

Alfa AF: 0.337 Hom.: 18158

Bravo AF: 0.397

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.63
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1867631; hg19: chr1-67046126;