rs1325268

Variant names:

• chr1-66695298-C-T
• rs1325268
• NM_032291.4:c.1571-136C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032291.4(SGIP1):​c.1571-136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,429,936 control chromosomes in the GnomAD database, including 65,259 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 0.29 (6117 hom., cov: 27)
  • Exomes 𝑓: 0.30 (59142 hom.)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGIP1	NM_032291.4	c.1571-136C>T		intron_variant	Intron 17 of 24	ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9	c.1571-136C>T		intron_variant	Intron 17 of 24	1	NM_032291.4	ENSP00000360076.3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 41711 AN: 145822 Hom.: 6116 Cov.: 27

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.300 AC: 385077 AN: 1284028 Hom.: 59142 Cov.: 30 AF XY: 0.301 AC XY: 188803 AN XY: 627374

African (AFR) AF: 0.260 AC: 6990 AN: 26834

American (AMR) AF: 0.290 AC: 6893 AN: 23800

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 4568 AN: 21582

East Asian (EAS) AF: 0.244 AC: 7363 AN: 30224

South Asian (SAS) AF: 0.338 AC: 18554 AN: 54942

European-Finnish (FIN) AF: 0.270 AC: 12862 AN: 47664

Middle Eastern (MID) AF: 0.312 AC: 1598 AN: 5130

European-Non Finnish (NFE) AF: 0.304 AC: 310868 AN: 1021126

Other (OTH) AF: 0.292 AC: 15381 AN: 52726

GnomAD4 genome AF: 0.286 AC: 41721 AN: 145908 Hom.: 6117 Cov.: 27 AF XY: 0.282 AC XY: 20005 AN XY: 70942

African (AFR) AF: 0.262 AC: 10249 AN: 39088

American (AMR) AF: 0.308 AC: 4529 AN: 14682

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 736 AN: 3404

East Asian (EAS) AF: 0.212 AC: 1038 AN: 4904

South Asian (SAS) AF: 0.323 AC: 1457 AN: 4504

European-Finnish (FIN) AF: 0.259 AC: 2422 AN: 9364

Middle Eastern (MID) AF: 0.278 AC: 79 AN: 284

European-Non Finnish (NFE) AF: 0.304 AC: 20295 AN: 66740

Other (OTH) AF: 0.301 AC: 613 AN: 2038

Alfa AF: 0.295 Hom.: 3426

Bravo AF: 0.288

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		3.4
Mutation Taster		=293/7	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: rs1325268; hg19: chr1-67160981; COSMIC: COSV52763189; COSMIC: COSV52763189;