rs2271205

Positions:

• chr3-9037765-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014850.4(SRGAP3):​c.1436+298C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 500,372 control chromosomes in the GnomAD database, including 16,455 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 0.24 (4452 hom., cov: 33)
  • Exomes 𝑓: 0.26 (12003 hom.)
• Consequence: SRGAP3 NM_014850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

Genes affected

SRGAP3 (HGNC:19744): (SLIT-ROBO Rho GTPase activating protein 3) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of cell migration. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP3	NM_014850.4	c.1436+298C>G		intron_variant		ENST00000383836.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP3	ENST00000383836.8	c.1436+298C>G		intron_variant		1	NM_014850.4	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36632 AN: 152018 Hom.: 4451 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.256 AC: 89271 AN: 348236 Hom.: 12003 Cov.: 2 AF XY: 0.262 AC XY: 48121 AN XY: 183632

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.241 AC: 36646 AN: 152136 Hom.: 4452 Cov.: 33 AF XY: 0.239 AC XY: 17795 AN XY: 74372

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.240

Alfa AF: 0.251 Hom.: 624

Bravo AF: 0.230

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2271205; hg19: chr3-9079449;