chr3-319864-T-G

Variant names:

• chr3-319864-T-G
• rs116261368
• NM_006614.4:c.88T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006614.4(CHL1):​c.88T>G​(p.Ser30Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00205 in 1,559,796 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (25 hom.)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.38
• Publications: 3 publications found

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

CHL1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• partial deletion of the short arm of chromosome 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055780113).
• BP6: Variant 3-319864-T-G is Benign according to our data. Variant chr3-319864-T-G is described in ClinVar as Benign. ClinVar VariationId is 767882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00894 (1360/152136) while in subpopulation AFR AF = 0.03 (1245/41546). AF 95% confidence interval is 0.0286. There are 19 homozygotes in GnomAd4. There are 656 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1360 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006614.4. 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
	CHL1	NM_006614.4	MANE Select	c.88T>G	p.Ser30Ala	missense	Exon 3 of 28	NP_006605.2
	CHL1	NM_001253387.2		c.88T>G	p.Ser30Ala	missense	Exon 3 of 27	NP_001240316.1	O00533-1
	CHL1	NM_001253388.1		c.88T>G	p.Ser30Ala	missense	Exon 1 of 25	NP_001240317.1	A0A087X0M8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHL1	ENST00000256509.7	TSL:1 MANE Select	c.88T>G	p.Ser30Ala	missense	Exon 3 of 28	ENSP00000256509.2	O00533-2
	CHL1	ENST00000397491.6	TSL:1	c.88T>G	p.Ser30Ala	missense	Exon 3 of 27	ENSP00000380628.2	O00533-1
	CHL1	ENST00000620033.4	TSL:1	c.88T>G	p.Ser30Ala	missense	Exon 1 of 25	ENSP00000483512.1	A0A087X0M8

Frequencies

GnomAD3 genomes AF: 0.00885 AC: 1345 AN: 152018 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00289 AC: 706 AN: 243914 AF XY: 0.00279

Gnomad AFR exome AF: 0.0277

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000815

Gnomad OTH exome AF: 0.000841

GnomAD4 exome AF: 0.00130 AC: 1834 AN: 1407660 Hom.: 25 Cov.: 23 AF XY: 0.00140 AC XY: 983 AN XY: 703088

African (AFR) AF: 0.0304 AC: 955 AN: 31450

American (AMR) AF: 0.00125 AC: 55 AN: 44062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25590

East Asian (EAS) AF: 0.00420 AC: 165 AN: 39268

South Asian (SAS) AF: 0.00587 AC: 495 AN: 84342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52306

Middle Eastern (MID) AF: 0.00195 AC: 11 AN: 5646

European-Non Finnish (NFE) AF: 0.0000291 AC: 31 AN: 1066578

Other (OTH) AF: 0.00209 AC: 122 AN: 58418

GnomAD4 genome AF: 0.00894 AC: 1360 AN: 152136 Hom.: 19 Cov.: 32 AF XY: 0.00882 AC XY: 656 AN XY: 74362

African (AFR) AF: 0.0300 AC: 1245 AN: 41546

American (AMR) AF: 0.00275 AC: 42 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5160

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67954

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00301 Hom.: 10

Bravo AF: 0.00984

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00361 AC: 437

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.91	T
PhyloP100		4.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Benign	0.58	T
Polyphen		0.035	B
Vest4		0.44
MVP		0.65
MPC		0.012
ClinPred		0.0090	T
GERP RS		4.9
PromoterAI		-0.018	Neutral
Varity_R		0.16
gMVP		0.17
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: rs116261368; hg19: chr3-361547;