Genetic Variant SPRING1:p.Leu89Leu (chr12-116723068-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024738.4(SPRING1):c.267C>T(p.Leu89Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,612,334 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 74 hom. )

Consequence

SPRING1
NM_024738.4 splice_region, synonymous

Scores

Splicing: ADA: 0.001819

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

SPRING1 (HGNC:26128): (SREBF pathway regulator in golgi 1) Involved in positive regulation of SREBP signaling pathway. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPRING1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-116723068-G-A is Benign according to our data. Variant chr12-116723068-G-A is described in ClinVar as [Benign]. Clinvar id is 782333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRING1	NM_024738.4 link	c.267C>T	p.Leu89Leu	splice_region_variant, synonymous_variant	Exon 2 of 5	ENST00000261318.5	NP_079014.1	Q9H741A0A024RBQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPRING1	ENST00000261318.5 link	c.267C>T	p.Leu89Leu	splice_region_variant, synonymous_variant	Exon 2 of 5	1	NM_024738.4	ENSP00000261318.3	Q9H741
SPRING1	ENST00000547630.1 link	n.112-2621C>T		intron_variant	Intron 1 of 3	1		ENSP00000446478.1	F8VPB4
SPRING1	ENST00000547606.1 link	c.46-5175C>T		intron_variant	Intron 1 of 1	3		ENSP00000447722.1	H0YHS8

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1060

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00751

AC:

1888

AN:

251266

Hom.:

AF XY:

0.00730

AC XY:

991

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.00976

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00797

AC:

11643

AN:

1459970

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

5521

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.00854

Gnomad4 OTH exome

AF:

0.00759

GnomAD4 genome

AF:

0.00696

AC:

1060

AN:

152364

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0203

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.00510

EpiCase

AF:

0.00845

EpiControl

AF:

0.00984

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 12, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0018

dbscSNV1_RF

Benign

0.088

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over