rs2146904

Variant names:

• chr1-66694653-A-G
• rs2146904
• NM_032291.4:c.1571-781A>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.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
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.972 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	NM_032291.4	MANE Select	c.1571-781A>G		intron	N/A	NP_115667.2	Q9BQI5-1
	SGIP1	NM_001350217.2		c.1583-781A>G		intron	N/A	NP_001337146.1	Q9BQI5-2
	SGIP1	NM_001376534.1		c.1571-781A>G		intron	N/A	NP_001363463.1	Q9BQI5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	ENST00000371037.9	TSL:1 MANE Select	c.1571-781A>G		intron	N/A	ENSP00000360076.3	Q9BQI5-1
	SGIP1	ENST00000371039.5	TSL:1	c.1039+149A>G		intron	N/A	ENSP00000360078.1	Q9BQI5-5
	SGIP1	ENST00000237247.10	TSL:5	c.1664-781A>G		intron	N/A	ENSP00000237247.6	Q9BQI5-3

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

African (AFR) AF: 0.638 AC: 5403 AN: 8470

American (AMR) AF: 0.732 AC: 6466 AN: 8828

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 6236 AN: 9976

East Asian (EAS) AF: 0.998 AC: 23282 AN: 23328

South Asian (SAS) AF: 0.804 AC: 6434 AN: 7998

European-Finnish (FIN) AF: 0.549 AC: 12776 AN: 23264

Middle Eastern (MID) AF: 0.694 AC: 2183 AN: 3144

European-Non Finnish (NFE) AF: 0.564 AC: 132452 AN: 234688

Other (OTH) AF: 0.634 AC: 12614 AN: 19882

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

African (AFR) AF: 0.644 AC: 26682 AN: 41444

American (AMR) AF: 0.710 AC: 10841 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3468

East Asian (EAS) AF: 0.995 AC: 5145 AN: 5172

South Asian (SAS) AF: 0.811 AC: 3891 AN: 4800

European-Finnish (FIN) AF: 0.544 AC: 5738 AN: 10556

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38415 AN: 67962

Other (OTH) AF: 0.620 AC: 1306 AN: 2108

Alfa AF: 0.600 Hom.: 15452

Bravo AF: 0.638

Asia WGS AF: 0.876 AC: 3047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.020
DANN	Benign	0.45
PhyloP100		-0.99
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: rs2146904; hg19: chr1-67160336;