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GeneBe

3-47414240-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_012235.4(SCAP):c.3534G>A(p.Leu1178=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,670 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 17 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 26 hom. )

Consequence

SCAP
NM_012235.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.360
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 -13 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=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-47414240-C-T is Benign according to our data. Variant chr3-47414240-C-T is described in ClinVar as [Benign]. Clinvar id is 789983.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=0.36 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00907 (1381/152306) while in subpopulation AFR AF= 0.0315 (1310/41556). AF 95% confidence interval is 0.0301. There are 17 homozygotes in gnomad4. There are 661 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
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 17 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAPNM_012235.4 linkuse as main transcriptc.3534G>A p.Leu1178= synonymous_variant 22/23 ENST00000265565.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAPENST00000265565.10 linkuse as main transcriptc.3534G>A p.Leu1178= synonymous_variant 22/231 NM_012235.4 P1Q12770-1
SCAPENST00000648151.1 linkuse as main transcriptc.3534G>A p.Leu1178= synonymous_variant 23/24 P1Q12770-1
SCAPENST00000320017.10 linkuse as main transcriptc.*2248G>A 3_prime_UTR_variant, NMD_transcript_variant 17/182
SCAPENST00000441517.6 linkuse as main transcriptc.*2680G>A 3_prime_UTR_variant, NMD_transcript_variant 19/202

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00905
AC:
1378
AN:
152188
Hom.:
17
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0315
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00321
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00223
AC:
560
AN:
250682
Hom.:
7
AF XY:
0.00170
AC XY:
230
AN XY:
135686
show subpopulations
Gnomad AFR exome
AF:
0.0288
Gnomad AMR exome
AF:
0.00156
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00108
AC:
1578
AN:
1461364
Hom.:
26
Cov.:
32
AF XY:
0.000979
AC XY:
712
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.0346
Gnomad4 AMR exome
AF:
0.00181
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000133
Gnomad4 OTH exome
AF:
0.00275
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00907
AC:
1381
AN:
152306
Hom.:
17
Cov.:
33
AF XY:
0.00888
AC XY:
661
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0315
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00268
Hom.:
8
Bravo
AF:
0.0101
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

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 testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
3.1
Dann
Benign
0.80
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: rs35628908; hg19: chr3-47455730; API