1-11706436-C-T

Variant names:

• chr1-11706436-C-T
• rs202026446
• NM_198545.4:c.178C>T

Variant summary

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

The NM_198545.4(DRAXIN):​c.178C>T​(p.Arg60Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,611,554 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0045 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (29 hom.)
• Consequence: DRAXIN NM_198545.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.00
• Publications: 10 publications found

Genes affected

DRAXIN (HGNC:25054): (dorsal inhibitory axon guidance protein) Predicted to be involved in negative regulation of canonical Wnt signaling pathway; negative regulation of neuron projection development; and nervous system development. Predicted to act upstream of or within negative regulation of axon extension and negative regulation of neuron apoptotic process. Predicted to be active in extracellular region. [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 (MetaRNN=0.0045908093).
• BP6: Variant 1-11706436-C-T is Benign according to our data. Variant chr1-11706436-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198545.4. 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
	DRAXIN	NM_198545.4	MANE Select	c.178C>T	p.Arg60Trp	missense	Exon 2 of 7	NP_940947.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRAXIN	ENST00000294485.6	TSL:1 MANE Select	c.178C>T	p.Arg60Trp	missense	Exon 2 of 7	ENSP00000294485.5	Q8NBI3
	DRAXIN	ENST00000855916.1		c.178C>T	p.Arg60Trp	missense	Exon 2 of 7	ENSP00000525975.1
	DRAXIN	ENST00000911392.1		c.178C>T	p.Arg60Trp	missense	Exon 3 of 8	ENSP00000581451.1

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 687 AN: 152200 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00373 AC: 893 AN: 239620 AF XY: 0.00405

Gnomad AFR exome AF: 0.000774

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00779

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.000620

Gnomad NFE exome AF: 0.00536

Gnomad OTH exome AF: 0.00445

GnomAD4 exome AF: 0.00485 AC: 7075 AN: 1459236 Hom.: 29 Cov.: 33 AF XY: 0.00496 AC XY: 3600 AN XY: 725894

African (AFR) AF: 0.000897 AC: 30 AN: 33430

American (AMR) AF: 0.00226 AC: 101 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00694 AC: 181 AN: 26064

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39668

South Asian (SAS) AF: 0.00411 AC: 354 AN: 86090

European-Finnish (FIN) AF: 0.000950 AC: 50 AN: 52624

Middle Eastern (MID) AF: 0.00443 AC: 23 AN: 5196

European-Non Finnish (NFE) AF: 0.00549 AC: 6100 AN: 1111344

Other (OTH) AF: 0.00389 AC: 234 AN: 60182

GnomAD4 genome AF: 0.00451 AC: 687 AN: 152318 Hom.: 18 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74476

African (AFR) AF: 0.00113 AC: 47 AN: 41578

American (AMR) AF: 0.00170 AC: 26 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00512 Hom.: 1

Bravo AF: 0.00501

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00139 AC: 6

ESP6500EA AF: 0.00449 AC: 38

ExAC AF: 0.00376 AC: 453

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00706

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.0
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.095
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.49
MPC		0.82
ClinPred		0.025	T
GERP RS		3.8
Varity_R		0.16
gMVP		0.32
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs202026446; hg19: chr1-11766493; COSMIC: COSV53843331;