Genetic Variant NM_203349.4:c.585+16198G>A (chr15-48946233-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_203349.4(SHC4):c.585+16198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,066 control chromosomes in the GnomAD database, including 15,663 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 0.44 ( 15663 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SHC4
NM_203349.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.767

Publications

6 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]

SHC4 links:

ENSG00000259602 (HGNC:):

ENSG00000259602 links:

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=-0.49).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4 link	c.585+16198G>A		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3	Q6S5L8-1
SHC4	XM_005254375.4 link	c.36+327G>A		intron_variant	Intron 1 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9 link	c.585+16198G>A		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4		Q6S5L8-1
ENSG00000259602	ENST00000559620.1 link	n.316+103C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67620

AN:

151948

Hom.:

15658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.504

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.445

AC:

67660

AN:

152066

Hom.:

15663

Cov.:

AF XY:

0.442

AC XY:

32826

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.317

AC:

13145

AN:

41476

American (AMR)

AF:

0.443

AC:

6762

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2115

AN:

3470

East Asian (EAS)

AF:

0.509

AC:

2634

AN:

5170

South Asian (SAS)

AF:

0.493

AC:

2377

AN:

4824

European-Finnish (FIN)

AF:

0.402

AC:

4251

AN:

10572

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34477

AN:

67968

Other (OTH)

AF:

0.501

AC:

1055

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1895

3791

5686

7582

9477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.498

Hom.:

18564

Bravo

AF:

0.445

Asia WGS

AF:

0.441

AC:

1535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over