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GeneBe

19-49645071-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021228.3(SCAF1):c.45G>C(p.Gly15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,154 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 36 hom. )

Consequence

SCAF1
NM_021228.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.902
Variant links:
Genes affected
SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-49645071-G-C is Benign according to our data. Variant chr19-49645071-G-C is described in ClinVar as [Benign]. Clinvar id is 769038.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=-0.902 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 = 0.0115 (1752/152320) while in subpopulation AFR AF= 0.0394 (1639/41568). AF 95% confidence interval is 0.0378. There are 28 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 26 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF1NM_021228.3 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 2/11 ENST00000360565.8
SCAF1XM_011527194.4 linkuse as main transcriptc.54G>C p.Gly18= synonymous_variant 2/11
SCAF1XM_005259122.6 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF1ENST00000360565.8 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 2/112 NM_021228.3 P1
SCAF1ENST00000598359.5 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 2/73
SCAF1ENST00000595242.3 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 1/43
SCAF1ENST00000601038.5 linkuse as main transcriptc.45G>C p.Gly15= synonymous_variant 1/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0115
AC:
1744
AN:
152202
Hom.:
26
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0394
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00543
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00309
AC:
775
AN:
251096
Hom.:
11
AF XY:
0.00231
AC XY:
314
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.0400
Gnomad AMR exome
AF:
0.00232
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00124
AC:
1813
AN:
1461834
Hom.:
36
Cov.:
31
AF XY:
0.00109
AC XY:
793
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0420
Gnomad4 AMR exome
AF:
0.00282
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000728
Gnomad4 OTH exome
AF:
0.00277
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0115
AC:
1752
AN:
152320
Hom.:
28
Cov.:
32
AF XY:
0.0113
AC XY:
838
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0394
Gnomad4 AMR
AF:
0.00543
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.000763
Hom.:
0
Bravo
AF:
0.0129
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000415

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 testingInvitaeJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
4.4
Dann
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs114682662; hg19: chr19-50148328; API