rs3790557

Positions:

• chr1-67419714-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001018069.2(SERBP1):​c.951+295C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 288,510 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0059 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (12 hom.)
• Consequence: SERBP1 NM_001018069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

SERBP1 (HGNC:17860): (SERPINE1 mRNA binding protein 1) Enables SUMO binding activity; mRNA 3'-UTR binding activity; and ribosome binding activity. Involved in PML body organization. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00589 (896/152164) while in subpopulation EAS AF= 0.0437 (226/5176). AF 95% confidence interval is 0.039. There are 13 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 896 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERBP1	NM_001018069.2	c.951+295C>G		intron_variant		ENST00000361219.11	NP_001018079.1
SERBP1	NM_001018067.2	c.996+295C>G		intron_variant			NP_001018077.1
SERBP1	NM_001018068.2	c.978+295C>G		intron_variant			NP_001018078.1
SERBP1	NM_015640.4	c.933+295C>G		intron_variant			NP_056455.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERBP1	ENST00000361219.11	c.951+295C>G		intron_variant		1	NM_001018069.2	ENSP00000354591

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152046 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00596 AC: 812 AN: 136346 Hom.: 12 AF XY: 0.00547 AC XY: 395 AN XY: 72254

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00165

Gnomad4 EAS exome AF: 0.0418

Gnomad4 SAS exome AF: 0.000724

Gnomad4 FIN exome AF: 0.00576

Gnomad4 NFE exome AF: 0.00399

Gnomad4 OTH exome AF: 0.00869

GnomAD4 genome AF: 0.00589 AC: 896 AN: 152164 Hom.: 13 Cov.: 32 AF XY: 0.00591 AC XY: 440 AN XY: 74400

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0437

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00727

Gnomad4 NFE AF: 0.00497

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00842 Hom.: 0

Bravo AF: 0.00605

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs3790557; hg19: chr1-67885397;