1-66657374-A-G

Variant names:

• chr1-66657374-A-G
• rs6681460
• NM_032291.4:c.460-3139A>G

Variant summary

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

The NM_032291.4(SGIP1):​c.460-3139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,928 control chromosomes in the GnomAD database, including 32,826 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 0.65 (32826 hom., cov: 31)
• Consequence: SGIP1 NM_032291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	NM_032291.4	MANE Select	c.460-3139A>G		intron	N/A	NP_115667.2
	SGIP1	NM_001350217.2		c.472-3139A>G		intron	N/A	NP_001337146.1
	SGIP1	NM_001376534.1		c.460-3139A>G		intron	N/A	NP_001363463.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	ENST00000371037.9	TSL:1 MANE Select	c.460-3139A>G		intron	N/A	ENSP00000360076.3
	SGIP1	ENST00000371039.5	TSL:1	c.388-13621A>G		intron	N/A	ENSP00000360078.1
	SGIP1	ENST00000237247.10	TSL:5	c.472-3139A>G		intron	N/A	ENSP00000237247.6

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98340 AN: 151810 Hom.: 32785 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.648 AC: 98443 AN: 151928 Hom.: 32826 Cov.: 31 AF XY: 0.650 AC XY: 48265 AN XY: 74244

African (AFR) AF: 0.714 AC: 29596 AN: 41428

American (AMR) AF: 0.717 AC: 10939 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5157 AN: 5166

South Asian (SAS) AF: 0.887 AC: 4274 AN: 4818

European-Finnish (FIN) AF: 0.519 AC: 5456 AN: 10514

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38785 AN: 67960

Other (OTH) AF: 0.636 AC: 1341 AN: 2108

Alfa AF: 0.602 Hom.: 88630

Bravo AF: 0.661

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.1
DANN	Benign	0.43
PhyloP100		0.16
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: rs6681460; hg19: chr1-67123057;