Genetic Variant SRGAP1:p.Leu49Leu (chr12-63984024-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020762.4(SRGAP1):c.145C>T(p.Leu49Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,577,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

SRGAP1
NM_020762.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.73

Publications

0 publications found

Variant links:

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)

SRGAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 12-63984024-C-T is Benign according to our data. Variant chr12-63984024-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 725157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.73 with no splicing effect.

BS2

High AC in GnomAd4 at 55 AD gene.

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.145C>T	p.Leu49Leu	synonymous	Exon 2 of 22	NP_065813.1	Q7Z6B7-1
	SRGAP1	NM_001346201.2		c.145C>T	p.Leu49Leu	synonymous	Exon 2 of 22	NP_001333130.1	Q7Z6B7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGAP1	ENST00000355086.8	TSL:1 MANE Select	c.145C>T	p.Leu49Leu	synonymous	Exon 2 of 22	ENSP00000347198.3	Q7Z6B7-1
SRGAP1	ENST00000543397.1	TSL:1	n.1500C>T		non_coding_transcript_exon	Exon 1 of 21
SRGAP1	ENST00000875666.1		c.145C>T	p.Leu49Leu	synonymous	Exon 2 of 21	ENSP00000545725.1

Frequencies

GnomAD3 genomes

AF:

0.000364

AC:

AN:

151122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000632

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000649

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000513

AC:

124

AN:

241682

AF XY:

0.000549

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.000186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.000519

GnomAD4 exome

AF:

0.000623

AC:

889

AN:

1426578

Hom.:

Cov.:

AF XY:

0.000643

AC XY:

456

AN XY:

709594

show subpopulations

African (AFR)

AF:

0.0000920

AC:

AN:

32592

American (AMR)

AF:

0.000139

AC:

AN:

43060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

38496

South Asian (SAS)

AF:

0.00166

AC:

134

AN:

80960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52564

Middle Eastern (MID)

AF:

0.000356

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.000654

AC:

713

AN:

1089696

Other (OTH)

AF:

0.000530

AC:

AN:

58452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000364

AC:

AN:

151236

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

73806

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

41230

American (AMR)

AF:

0.00

AC:

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.000632

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000649

AC:

AN:

67810

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000307

Hom.:

Bravo

AF:

0.000310

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over