rs6717394

Variant names:

• chr2-219551112-A-G
• rs6717394
• NM_015311.3:c.5684-270T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-219551112-A-G
• chr2-219551112-A-T

Variant summary

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

The NM_015311.3(OBSL1):​c.5684-270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,402,120 control chromosomes in the GnomAD database, including 680,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67965 hom., cov: 31)
  • Exomes 𝑓: 0.99 (612055 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49
• Publications: 1 publications found

Genes affected

OBSL1 (HGNC:29092): (obscurin like cytoskeletal adaptor 1) Cytoskeletal adaptor proteins function in linking the internal cytoskeleton of cells to the cell membrane. This gene encodes a cytoskeletal adaptor protein, which is a member of the Unc-89/obscurin family. The protein contains multiple N- and C-terminal immunoglobulin (Ig)-like domains and a central fibronectin type 3 domain. Mutations in this gene cause 3M syndrome type 2. Alternatively spliced transcript variants encoding different isoforms have been found in this gene. [provided by RefSeq, Mar 2010]

OBSL1 Gene-Disease associations (from GenCC):

• 3M syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 3-M syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-219551112-A-G is Benign according to our data. Variant chr2-219551112-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015311.3. 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
	OBSL1	NM_015311.3	MANE Select	c.5684-270T>C		intron	N/A	NP_056126.1	O75147-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	ENST00000404537.6	TSL:1 MANE Select	c.5684-270T>C		intron	N/A	ENSP00000385636.1	O75147-3
	OBSL1	ENST00000953546.1		c.5696-270T>C		intron	N/A	ENSP00000623605.1
	OBSL1	ENST00000953548.1		c.5627-270T>C		intron	N/A	ENSP00000623607.1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143251 AN: 152026 Hom.: 67939 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.955

GnomAD4 exome AF: 0.989 AC: 1236402 AN: 1249976 Hom.: 612055 Cov.: 44 AF XY: 0.990 AC XY: 597141 AN XY: 603372

African (AFR) AF: 0.803 AC: 22212 AN: 27656

American (AMR) AF: 0.978 AC: 18476 AN: 18894

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 18012 AN: 18094

East Asian (EAS) AF: 1.00 AC: 32770 AN: 32772

South Asian (SAS) AF: 0.999 AC: 58564 AN: 58620

European-Finnish (FIN) AF: 0.994 AC: 27283 AN: 27448

Middle Eastern (MID) AF: 0.976 AC: 3400 AN: 3484

European-Non Finnish (NFE) AF: 0.994 AC: 1004855 AN: 1011154

Other (OTH) AF: 0.980 AC: 50830 AN: 51854

GnomAD4 genome AF: 0.942 AC: 143333 AN: 152144 Hom.: 67965 Cov.: 31 AF XY: 0.943 AC XY: 70140 AN XY: 74376

African (AFR) AF: 0.817 AC: 33868 AN: 41442

American (AMR) AF: 0.965 AC: 14756 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3446 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5165 AN: 5166

South Asian (SAS) AF: 0.999 AC: 4819 AN: 4824

European-Finnish (FIN) AF: 0.994 AC: 10546 AN: 10610

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67565 AN: 68018

Other (OTH) AF: 0.955 AC: 2019 AN: 2114

Alfa AF: 0.963 Hom.: 8810

Bravo AF: 0.935

Asia WGS AF: 0.983 AC: 3419 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.60
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6717394; hg19: chr2-220415834;