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GeneBe

3-47413929-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_012235.4(SCAP):c.3765C>T(p.Asn1255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,613,280 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 24 hom., cov: 32)
Exomes 𝑓: 0.0048 ( 80 hom. )

Consequence

SCAP
NM_012235.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-47413929-G-A is Benign according to our data. Variant chr3-47413929-G-A is described in ClinVar as [Benign]. Clinvar id is 790346.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-1 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 24 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAPNM_012235.4 linkuse as main transcriptc.3765C>T p.Asn1255= synonymous_variant 23/23 ENST00000265565.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAPENST00000265565.10 linkuse as main transcriptc.3765C>T p.Asn1255= synonymous_variant 23/231 NM_012235.4 P1Q12770-1
SCAPENST00000648151.1 linkuse as main transcriptc.3765C>T p.Asn1255= synonymous_variant 24/24 P1Q12770-1
SCAPENST00000320017.10 linkuse as main transcriptc.*2479C>T 3_prime_UTR_variant, NMD_transcript_variant 18/182
SCAPENST00000441517.6 linkuse as main transcriptc.*2911C>T 3_prime_UTR_variant, NMD_transcript_variant 20/202

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00699
AC:
1064
AN:
152170
Hom.:
24
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000627
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0403
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00819
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00687
AC:
1727
AN:
251220
Hom.:
31
AF XY:
0.00697
AC XY:
946
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00150
Gnomad ASJ exome
AF:
0.00228
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.000882
Gnomad FIN exome
AF:
0.0410
Gnomad NFE exome
AF:
0.00604
Gnomad OTH exome
AF:
0.00750
GnomAD4 exome
AF:
0.00482
AC:
7038
AN:
1460992
Hom.:
80
Cov.:
32
AF XY:
0.00497
AC XY:
3612
AN XY:
726806
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.00139
Gnomad4 ASJ exome
AF:
0.00268
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000939
Gnomad4 FIN exome
AF:
0.0383
Gnomad4 NFE exome
AF:
0.00413
Gnomad4 OTH exome
AF:
0.00349
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00699
AC:
1064
AN:
152288
Hom.:
24
Cov.:
32
AF XY:
0.00854
AC XY:
636
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0403
Gnomad4 NFE
AF:
0.00819
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00794
Hom.:
8
Bravo
AF:
0.00279
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00382
EpiControl
AF:
0.00338

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
0.23
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs112830289; hg19: chr3-47455419; COSMIC: COSV55544316; COSMIC: COSV55544316; API