Genetic Variant NM_024738.4:c.267C>T (chr12-116723068-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024738.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRING1	NM_024738.4	MANE Select	c.267C>T	p.Leu89Leu	splice_region synonymous	Exon 2 of 5	NP_079014.1	Q9H741
SPRING1	NM_001353623.2		c.179-2621C>T		intron	N/A	NP_001340552.1
SPRING1	NM_001353624.2		c.112-3192C>T		intron	N/A	NP_001340553.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRING1	ENST00000261318.5	TSL:1 MANE Select	c.267C>T	p.Leu89Leu	splice_region synonymous	Exon 2 of 5	ENSP00000261318.3	Q9H741
SPRING1	ENST00000547630.1	TSL:1	n.112-2621C>T		intron	N/A	ENSP00000446478.1	F8VPB4
SPRING1	ENST00000547606.1	TSL:3	c.46-5175C>T		intron	N/A	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

GnomAD2 exomes

AF:

0.00751

AC:

1888

AN:

251266

AF XY:

0.00730

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 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

African (AFR)

AF:

0.000928

AC:

AN:

33418

American (AMR)

AF:

0.00284

AC:

127

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

315

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00175

AC:

151

AN:

86172

European-Finnish (FIN)

AF:

0.0191

AC:

1021

AN:

53408

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

4210

European-Non Finnish (NFE)

AF:

0.00854

AC:

9491

AN:

1111982

Other (OTH)

AF:

0.00759

AC:

457

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

609

1218

1828

2437

3046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00696

AC:

1060

AN:

152364

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

41584

American (AMR)

AF:

0.00203

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0203

AC:

215

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0102

AC:

695

AN:

68044

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.00510

EpiCase

AF:

0.00845

EpiControl

AF:

0.00984

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

(source)

DANN

Benign

0.64

PhyloP100

-1.9

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over