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GeneBe

3-47414198-C-T

Variant summary

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

The NM_012235.4(SCAP):c.3576G>A(p.Lys1192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,752 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0061 ( 38 hom. )

Consequence

SCAP
NM_012235.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.719
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=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-47414198-C-T is Benign according to our data. Variant chr3-47414198-C-T is described in ClinVar as [Benign]. Clinvar id is 777773.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=0.719 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 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAPNM_012235.4 linkuse as main transcriptc.3576G>A p.Lys1192= synonymous_variant 22/23 ENST00000265565.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAPENST00000265565.10 linkuse as main transcriptc.3576G>A p.Lys1192= synonymous_variant 22/231 NM_012235.4 P1Q12770-1
SCAPENST00000648151.1 linkuse as main transcriptc.3576G>A p.Lys1192= synonymous_variant 23/24 P1Q12770-1
SCAPENST00000320017.10 linkuse as main transcriptc.*2290G>A 3_prime_UTR_variant, NMD_transcript_variant 17/182
SCAPENST00000441517.6 linkuse as main transcriptc.*2722G>A 3_prime_UTR_variant, NMD_transcript_variant 19/202

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00454
AC:
691
AN:
152208
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.0384
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00828
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00726
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00434
AC:
1089
AN:
250708
Hom.:
3
AF XY:
0.00443
AC XY:
601
AN XY:
135656
show subpopulations
Gnomad AFR exome
AF:
0.000680
Gnomad AMR exome
AF:
0.000926
Gnomad ASJ exome
AF:
0.00239
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00758
Gnomad NFE exome
AF:
0.00734
Gnomad OTH exome
AF:
0.00343
GnomAD4 exome
AF:
0.00606
AC:
8863
AN:
1461426
Hom.:
38
Cov.:
32
AF XY:
0.00590
AC XY:
4286
AN XY:
726988
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
Gnomad4 AMR exome
AF:
0.00103
Gnomad4 ASJ exome
AF:
0.00249
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00789
Gnomad4 NFE exome
AF:
0.00721
Gnomad4 OTH exome
AF:
0.00454
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00454
AC:
691
AN:
152326
Hom.:
4
Cov.:
33
AF XY:
0.00466
AC XY:
347
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00828
Gnomad4 NFE
AF:
0.00726
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00568
Hom.:
0
Bravo
AF:
0.00398
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00785
EpiControl
AF:
0.00533

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 07, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
5.0
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs151014440; hg19: chr3-47455688; API