11-125957023-A-G

Variant names:

• chr11-125957023-A-G
• rs61917811
• NM_001378964.1:c.*3919T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001378964.1(CDON):​c.*3919T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 238,100 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (3 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110
• Publications: 0 publications found

Genes affected

CDON (HGNC:17104): (cell adhesion associated, oncogene regulated) This gene encodes a cell surface receptor that is a member of the immunoglobulin superfamily. The encoded protein contains three fibronectin type III domains and five immunoglobulin-like C2-type domains. This protein is a member of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells and positively regulates myogenesis. [provided by RefSeq, Aug 2011]

VSIG10L2 (HGNC:27879): (V-set and immunoglobulin domain containing 10 like 2) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-125957023-A-G is Benign according to our data. Variant chr11-125957023-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 303376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 574 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. 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
	CDON	NM_001378964.1	MANE Select	c.*3919T>C		3_prime_UTR	Exon 20 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.*3919T>C		3_prime_UTR	Exon 20 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.*3919T>C		3_prime_UTR	Exon 20 of 20	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.*3919T>C		3_prime_UTR	Exon 20 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.*3919T>C		3_prime_UTR	Exon 20 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000684078.1		c.*3919T>C		3_prime_UTR	Exon 20 of 20	ENSP00000507318.1	Q4KMG0-1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152208 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00315 AC: 270 AN: 85774 Hom.: 3 Cov.: 5 AF XY: 0.00324 AC XY: 134 AN XY: 41338

African (AFR) AF: 0.00205 AC: 3 AN: 1466

American (AMR) AF: 0.0114 AC: 1 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 18 AN: 486

East Asian (EAS) AF: 0.00 AC: 0 AN: 340

South Asian (SAS) AF: 0.00121 AC: 2 AN: 1656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AF: 0.00562 AC: 1 AN: 178

European-Non Finnish (NFE) AF: 0.00293 AC: 231 AN: 78852

Other (OTH) AF: 0.00522 AC: 14 AN: 2682

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152326 Hom.: 3 Cov.: 33 AF XY: 0.00364 AC XY: 271 AN XY: 74486

African (AFR) AF: 0.000625 AC: 26 AN: 41574

American (AMR) AF: 0.00418 AC: 64 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00422 AC: 287 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00482 Hom.: 3

Bravo AF: 0.00400

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Holoprosencephaly 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		-0.011
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61917811; hg19: chr11-125826918;