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GeneBe

3-47414632-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_012235.4(SCAP):c.3327G>T(p.Ser1109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,613,330 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S1109S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0043 ( 19 hom. )

Consequence

SCAP
NM_012235.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.74
Variant links:
Genes affected
SCAP (HGNC:30634): (SREBF chaperone) This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-47414632-C-A is Benign according to our data. Variant chr3-47414632-C-A is described in ClinVar as [Benign]. Clinvar id is 772861.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-47414632-C-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.74 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAPNM_012235.4 linkuse as main transcriptc.3327G>T p.Ser1109= synonymous_variant 21/23 ENST00000265565.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAPENST00000265565.10 linkuse as main transcriptc.3327G>T p.Ser1109= synonymous_variant 21/231 NM_012235.4 P1Q12770-1
SCAPENST00000648151.1 linkuse as main transcriptc.3327G>T p.Ser1109= synonymous_variant 22/24 P1Q12770-1
SCAPENST00000320017.10 linkuse as main transcriptc.*2041G>T 3_prime_UTR_variant, NMD_transcript_variant 16/182
SCAPENST00000441517.6 linkuse as main transcriptc.*2473G>T 3_prime_UTR_variant, NMD_transcript_variant 18/202

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00288
AC:
439
AN:
152226
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000796
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00386
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00466
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00331
AC:
830
AN:
250748
Hom.:
3
AF XY:
0.00368
AC XY:
499
AN XY:
135708
show subpopulations
Gnomad AFR exome
AF:
0.000556
Gnomad AMR exome
AF:
0.00174
Gnomad ASJ exome
AF:
0.000896
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00278
Gnomad FIN exome
AF:
0.00462
Gnomad NFE exome
AF:
0.00481
Gnomad OTH exome
AF:
0.00376
GnomAD4 exome
AF:
0.00425
AC:
6212
AN:
1460986
Hom.:
19
Cov.:
32
AF XY:
0.00421
AC XY:
3060
AN XY:
726774
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.00170
Gnomad4 ASJ exome
AF:
0.00119
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00264
Gnomad4 FIN exome
AF:
0.00468
Gnomad4 NFE exome
AF:
0.00474
Gnomad4 OTH exome
AF:
0.00522
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00288
AC:
439
AN:
152344
Hom.:
2
Cov.:
32
AF XY:
0.00267
AC XY:
199
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000794
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.00386
Gnomad4 NFE
AF:
0.00466
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00317
Hom.:
2
Bravo
AF:
0.00245
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00562
EpiControl
AF:
0.00409

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
Cadd
Benign
6.9
Dann
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140861904; hg19: chr3-47456122; API