rs536410

Variant names:

• chr1-66725401-T-C
• rs536410
• NM_032291.4:c.1743-3863T>C

Variant summary

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

The NM_032291.4(SGIP1):​c.1743-3863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,064 control chromosomes in the GnomAD database, including 15,897 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 0.44 (15897 hom., cov: 32)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGIP1	NM_032291.4	c.1743-3863T>C		intron_variant	Intron 19 of 24	ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9	c.1743-3863T>C		intron_variant	Intron 19 of 24	1	NM_032291.4	ENSP00000360076.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66528 AN: 151944 Hom.: 15874 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.438 AC: 66597 AN: 152064 Hom.: 15897 Cov.: 32 AF XY: 0.433 AC XY: 32195 AN XY: 74332

African (AFR) AF: 0.578 AC: 23955 AN: 41462

American (AMR) AF: 0.308 AC: 4703 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3468

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5184

South Asian (SAS) AF: 0.190 AC: 916 AN: 4822

European-Finnish (FIN) AF: 0.457 AC: 4825 AN: 10554

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29650 AN: 67964

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.429 Hom.: 45623

Bravo AF: 0.434

Asia WGS AF: 0.140 AC: 489 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	3.4
DANN	Benign	0.67
PhyloP100		-0.47
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: rs536410; hg19: chr1-67191084; COSMIC: COSV52765070;