NM_001122955.4:c.766-49T>C

Variant names:

• chr11-62692522-A-G
• rs2850597
• NM_001122955.4:c.766-49T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122955.4(BSCL2):​c.766-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,609,882 control chromosomes in the GnomAD database, including 467,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43324 hom., cov: 31)
  • Exomes 𝑓: 0.76 (424409 hom.)
• Consequence: BSCL2 NM_001122955.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.240
• Publications: 12 publications found

Genes affected

BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]

HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-62692522-A-G is Benign according to our data. Variant chr11-62692522-A-G is described in ClinVar as Benign. ClinVar VariationId is 257500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122955.4. 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
	BSCL2	NM_001122955.4	MANE Select	c.766-49T>C		intron	N/A	NP_001116427.1	Q96G97-4
	BSCL2	NM_001386027.1		c.766-49T>C		intron	N/A	NP_001372956.1	J3KQ12
	BSCL2	NM_001386028.1		c.766-49T>C		intron	N/A	NP_001372957.1	Q96G97-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	ENST00000360796.10	TSL:1 MANE Select	c.766-49T>C		intron	N/A	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.766-49T>C		intron	N/A	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.574-49T>C		intron	N/A	ENSP00000384080.3	Q96G97-2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114452 AN: 151960 Hom.: 43300 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.754

GnomAD2 exomes AF: 0.781 AC: 192316 AN: 246176 AF XY: 0.781

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.772

Gnomad EAS exome AF: 0.769

Gnomad FIN exome AF: 0.848

Gnomad NFE exome AF: 0.761

Gnomad OTH exome AF: 0.792

GnomAD4 exome AF: 0.762 AC: 1111342 AN: 1457804 Hom.: 424409 Cov.: 35 AF XY: 0.764 AC XY: 553977 AN XY: 725170

African (AFR) AF: 0.663 AC: 22154 AN: 33430

American (AMR) AF: 0.846 AC: 37593 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 20165 AN: 26120

East Asian (EAS) AF: 0.747 AC: 29635 AN: 39662

South Asian (SAS) AF: 0.800 AC: 68940 AN: 86160

European-Finnish (FIN) AF: 0.844 AC: 44167 AN: 52322

Middle Eastern (MID) AF: 0.787 AC: 4516 AN: 5738

European-Non Finnish (NFE) AF: 0.755 AC: 837648 AN: 1109698

Other (OTH) AF: 0.772 AC: 46524 AN: 60250

GnomAD4 genome AF: 0.753 AC: 114525 AN: 152078 Hom.: 43324 Cov.: 31 AF XY: 0.759 AC XY: 56390 AN XY: 74326

African (AFR) AF: 0.675 AC: 27978 AN: 41458

American (AMR) AF: 0.830 AC: 12689 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2677 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3991 AN: 5170

South Asian (SAS) AF: 0.789 AC: 3803 AN: 4820

European-Finnish (FIN) AF: 0.854 AC: 9039 AN: 10590

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51797 AN: 67962

Other (OTH) AF: 0.752 AC: 1591 AN: 2116

Alfa AF: 0.762 Hom.: 9106

Bravo AF: 0.747

Asia WGS AF: 0.786 AC: 2732 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital generalized lipodystrophy type 2 (1)
-	-	1	Hereditary spastic paraplegia 17 (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5C (1)
-	-	1	not specified (1)
-	-	1	Severe neurodegenerative syndrome with lipodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.38
PhyloP100		0.24
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2850597; hg19: chr11-62459994;