NM_024738.4:c.267C>A

Variant names:

• chr12-116723068-G-T
• rs118149811
• NM_024738.4:c.267C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_024738.4(SPRING1):​c.267C>A​(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 0.0128 in 1,612,338 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L89L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0097 (12 hom., cov: 33)
  • Exomes 𝑓: 0.013 (167 hom.)
• Consequence: SPRING1 NM_024738.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001156
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.92 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 12 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRING1	ENST00000261318.5	TSL:1 MANE Select	c.267C>A	p.Leu89Leu	splice_region synonymous	Exon 2 of 5	ENSP00000261318.3	Q9H741
	SPRING1	ENST00000547630.1	TSL:1	n.112-2621C>A		intron	N/A	ENSP00000446478.1	F8VPB4
	SPRING1	ENST00000547606.1	TSL:3	c.46-5175C>A		intron	N/A	ENSP00000447722.1	H0YHS8

Frequencies

GnomAD3 genomes AF: 0.00970 AC: 1477 AN: 152246 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00986 AC: 2477 AN: 251266 AF XY: 0.00982

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00827

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0131 AC: 19106 AN: 1459974 Hom.: 167 Cov.: 31 AF XY: 0.0128 AC XY: 9313 AN XY: 726302

African (AFR) AF: 0.00299 AC: 100 AN: 33418

American (AMR) AF: 0.00832 AC: 372 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 308 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00657 AC: 566 AN: 86172

European-Finnish (FIN) AF: 0.00339 AC: 181 AN: 53412

Middle Eastern (MID) AF: 0.0164 AC: 69 AN: 4210

European-Non Finnish (NFE) AF: 0.0151 AC: 16778 AN: 1111984

Other (OTH) AF: 0.0122 AC: 732 AN: 60218

GnomAD4 genome AF: 0.00969 AC: 1477 AN: 152364 Hom.: 12 Cov.: 33 AF XY: 0.00965 AC XY: 719 AN XY: 74498

African (AFR) AF: 0.00310 AC: 129 AN: 41584

American (AMR) AF: 0.0118 AC: 181 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1025 AN: 68044

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00232 Hom.: 58

Bravo AF: 0.00996

EpiCase AF: 0.0150

EpiControl AF: 0.0152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.55
DANN	Benign	0.61
PhyloP100		-1.9
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.098
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

Other links and lift over

dbSNP: rs118149811; hg19: chr12-117160873; COSMIC: COSV99039436; COSMIC: COSV99039436;