Genetic Variant NM_024745.5:c.1517G>A (chr16-46584037-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024745.5(SHCBP1):c.1517G>A(p.Gly506Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,607,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SHCBP1
NM_024745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Publications

1 publications found

Variant links:

Genes affected

SHCBP1 (HGNC:29547): (SHC binding and spindle associated 1) Predicted to enable SH2 domain binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway and regulation of neural precursor cell proliferation. Predicted to be located in cytoplasm; midbody; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

SHCBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19543338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024745.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SHCBP1	NM_024745.5	MANE Select	c.1517G>A	p.Gly506Glu	missense	Exon 11 of 13	NP_079021.4
SHCBP1	NM_001324318.2		c.1403G>A	p.Gly468Glu	missense	Exon 11 of 13	NP_001311247.1
SHCBP1	NM_001324319.2		c.1283G>A	p.Gly428Glu	missense	Exon 10 of 12	NP_001311248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHCBP1	ENST00000303383.8	TSL:1 MANE Select	c.1517G>A	p.Gly506Glu	missense	Exon 11 of 13	ENSP00000306473.3	Q8NEM2
SHCBP1	ENST00000939745.1		c.1349G>A	p.Gly450Glu	missense	Exon 10 of 12	ENSP00000609804.1
SHCBP1	ENST00000567698.1	TSL:2	n.217G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000953

AC:

AN:

241328

AF XY:

0.000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000142

AC:

207

AN:

1455098

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

723070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33418

American (AMR)

AF:

0.0000454

AC:

AN:

44026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25808

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.000271

AC:

AN:

84722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53048

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000131

AC:

145

AN:

1108528

Other (OTH)

AF:

0.000183

AC:

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000164

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41530

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68014

Other (OTH)

AF:

0.000474

AC:

AN:

2110

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:

0.000138

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000907

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.025

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

M_CAP

Benign

0.021

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.93

PhyloP100

3.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.2

REVEL

Benign

0.27

Sift

Benign

0.96

Sift4G

Pathogenic

0.0

Polyphen

0.29

Vest4

0.30

MVP

0.73

MPC

0.33

ClinPred

0.080

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.88

Mutation Taster

=74/26

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