chr22-41235196-C-G

Variant names:

• chr22-41235196-C-G
• rs758093565
• NM_138481.2:c.2211G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138481.2(CHADL):​c.2211G>C​(p.Arg737Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,551,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: CHADL NM_138481.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860
• Publications: 0 publications found

Genes affected

CHADL (HGNC:25165): (chondroadherin like) Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060763657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138481.2. 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
	CHADL	NM_138481.2	MANE Select	c.2211G>C	p.Arg737Ser	missense	Exon 5 of 6	NP_612490.1	Q6NUI6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHADL	ENST00000216241.14	TSL:1 MANE Select	c.2211G>C	p.Arg737Ser	missense	Exon 5 of 6	ENSP00000216241.9	Q6NUI6-1
	CHADL	ENST00000892871.1		c.2190G>C	p.Arg730Ser	missense	Exon 5 of 6	ENSP00000562930.1
	CHADL	ENST00000892870.1		c.810G>C	p.Arg270Ser	missense	Exon 5 of 6	ENSP00000562929.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000322 AC: 5 AN: 155430 AF XY: 0.0000243

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000830

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000550 AC: 77 AN: 1399218 Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 37 AN XY: 690138

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 49070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000686 AC: 74 AN: 1078984

Other (OTH) AF: 0.0000345 AC: 2 AN: 58008

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000351 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.3
DANN	Benign	0.85
DEOGEN2	Benign	0.00091	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.086
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.47	T
Sift4G	Uncertain	0.038	D
Polyphen		0.020	B
Vest4		0.11
MutPred		0.29		Gain of phosphorylation at R737 (P = 0.0069)
MVP		0.076
MPC		0.025
ClinPred		0.034	T
GERP RS		-2.0
Varity_R		0.097
gMVP		0.43
Mutation Taster		=98/2	polymorphism

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: rs758093565; hg19: chr22-41631200;