rs17382306

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203349.4(SHC4):​c.1304-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,972 control chromosomes in the GnomAD database, including 2,374 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 0.17 ( 2374 hom., cov: 32)

Consequence

SHC4
NM_203349.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.144

Publications

0 publications found
Variant links:
Genes affected
SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHC4NM_203349.4 linkc.1304-241C>T intron_variant Intron 9 of 11 ENST00000332408.9 NP_976224.3 Q6S5L8-1
SHC4XM_005254375.4 linkc.755-241C>T intron_variant Intron 9 of 11 XP_005254432.1
SHC4XM_047432492.1 linkc.446-241C>T intron_variant Intron 6 of 8 XP_047288448.1
SHC4XM_047432493.1 linkc.446-241C>T intron_variant Intron 7 of 9 XP_047288449.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHC4ENST00000332408.9 linkc.1304-241C>T intron_variant Intron 9 of 11 1 NM_203349.4 ENSP00000329668.4 Q6S5L8-1
SHC4ENST00000396535.7 linkc.575-241C>T intron_variant Intron 6 of 8 1 ENSP00000379786.3 Q6S5L8-2
SHC4ENST00000537958.5 linkc.446-241C>T intron_variant Intron 7 of 9 2 ENSP00000443300.1 F5H5M1
SHC4ENST00000557797.5 linkn.385-241C>T intron_variant Intron 5 of 6 3 ENSP00000453344.1 H0YLU6

Frequencies

GnomAD3 genomes
AF:
0.168
AC:
25484
AN:
151854
Hom.:
2374
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.262
Gnomad AMR
AF:
0.149
Gnomad ASJ
AF:
0.199
Gnomad EAS
AF:
0.0803
Gnomad SAS
AF:
0.167
Gnomad FIN
AF:
0.196
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.212
Gnomad OTH
AF:
0.160
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.168
AC:
25506
AN:
151972
Hom.:
2374
Cov.:
32
AF XY:
0.166
AC XY:
12303
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.101
AC:
4179
AN:
41460
American (AMR)
AF:
0.150
AC:
2288
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.199
AC:
690
AN:
3472
East Asian (EAS)
AF:
0.0803
AC:
415
AN:
5170
South Asian (SAS)
AF:
0.167
AC:
805
AN:
4818
European-Finnish (FIN)
AF:
0.196
AC:
2061
AN:
10504
Middle Eastern (MID)
AF:
0.214
AC:
63
AN:
294
European-Non Finnish (NFE)
AF:
0.212
AC:
14432
AN:
67964
Other (OTH)
AF:
0.159
AC:
334
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1041
2081
3122
4162
5203
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
288
576
864
1152
1440
<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:
0.192
Hom.:
3876
Bravo
AF:
0.158
Asia WGS
AF:
0.153
AC:
534
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.2
DANN
Benign
0.69
PhyloP100
-0.14
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

Publications

Other links and lift over

dbSNP: rs17382306; hg19: chr15-49136026; API