rs11175219

Variant names:

• chr12-63968939-C-T
• rs11175219
• NM_020762.4:c.68-15008C>T

Variant summary

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

The NM_020762.4(SRGAP1):​c.68-15008C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,186 control chromosomes in the GnomAD database, including 636 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 0.080 (636 hom., cov: 32)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 7 publications found

Genes affected

SRGAP1 (HGNC:17382): (SLIT-ROBO Rho GTPase activating protein 1) The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42. [provided by RefSeq, Sep 2016]

SRGAP1 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• thyroid cancer, nonmedullary, 2

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020762.4. 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
	SRGAP1	NM_020762.4	MANE Select	c.68-15008C>T		intron	N/A	NP_065813.1	Q7Z6B7-1
	SRGAP1	NM_001346201.2		c.68-15008C>T		intron	N/A	NP_001333130.1	Q7Z6B7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP1	ENST00000355086.8	TSL:1 MANE Select	c.68-15008C>T		intron	N/A	ENSP00000347198.3	Q7Z6B7-1
	SRGAP1	ENST00000875666.1		c.68-15008C>T		intron	N/A	ENSP00000545725.1
	SRGAP1	ENST00000631006.3	TSL:5	c.68-15008C>T		intron	N/A	ENSP00000485752.2	Q7Z6B7-2

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12111 AN: 152068 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0797 AC: 12122 AN: 152186 Hom.: 636 Cov.: 32 AF XY: 0.0751 AC XY: 5584 AN XY: 74390

African (AFR) AF: 0.0221 AC: 917 AN: 41528

American (AMR) AF: 0.0491 AC: 751 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3468

East Asian (EAS) AF: 0.119 AC: 616 AN: 5172

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4822

European-Finnish (FIN) AF: 0.0653 AC: 692 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8420 AN: 67996

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.103 Hom.: 1680

Bravo AF: 0.0751

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.69
PhyloP100		0.42
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: rs11175219; hg19: chr12-64362719;