rs604737

Variant names:

• chr1-66743405-G-A
• rs604737
• NM_032291.4:c.*310G>A

Variant summary

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

The NM_001350217.2(SGIP1):​c.*310G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.187 in 238,498 control chromosomes in the GnomAD database, including 5,048 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 0.18 (3038 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2010 hom.)
• Consequence: SGIP1 NM_001350217.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350217.2. 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.*310G>A		3_prime_UTR	Exon 25 of 25	NP_115667.2
	SGIP1	NM_001350217.2		c.*310G>A		3_prime_UTR	Exon 25 of 25	NP_001337146.1
	SGIP1	NM_001376534.1		c.*310G>A		3_prime_UTR	Exon 26 of 26	NP_001363463.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	ENST00000371037.9	TSL:1 MANE Select	c.*310G>A		3_prime_UTR	Exon 25 of 25	ENSP00000360076.3
	SGIP1	ENST00000371039.5	TSL:1	c.*310G>A		3_prime_UTR	Exon 22 of 22	ENSP00000360078.1
	SGIP1	ENST00000237247.10	TSL:5	c.*310G>A		3_prime_UTR	Exon 27 of 27	ENSP00000237247.6

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27781 AN: 152020 Hom.: 3038 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.194 AC: 16759 AN: 86360 Hom.: 2010 Cov.: 0 AF XY: 0.182 AC XY: 8333 AN XY: 45692

African (AFR) AF: 0.110 AC: 305 AN: 2762

American (AMR) AF: 0.117 AC: 482 AN: 4134

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 453 AN: 2632

East Asian (EAS) AF: 0.000996 AC: 5 AN: 5020

South Asian (SAS) AF: 0.0788 AC: 811 AN: 10290

European-Finnish (FIN) AF: 0.293 AC: 1119 AN: 3816

Middle Eastern (MID) AF: 0.122 AC: 48 AN: 392

European-Non Finnish (NFE) AF: 0.239 AC: 12587 AN: 52556

Other (OTH) AF: 0.199 AC: 949 AN: 4758

GnomAD4 genome AF: 0.183 AC: 27775 AN: 152138 Hom.: 3038 Cov.: 32 AF XY: 0.182 AC XY: 13560 AN XY: 74368

African (AFR) AF: 0.107 AC: 4444 AN: 41520

American (AMR) AF: 0.129 AC: 1978 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3254 AN: 10582

Middle Eastern (MID) AF: 0.148 AC: 43 AN: 290

European-Non Finnish (NFE) AF: 0.243 AC: 16525 AN: 67944

Other (OTH) AF: 0.190 AC: 401 AN: 2112

Alfa AF: 0.218 Hom.: 12331

Bravo AF: 0.167

Asia WGS AF: 0.0460 AC: 160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		5.2
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: rs604737; hg19: chr1-67209088; COSMIC: COSV52765160;