1-109508840-C-T

Variant names:

• chr1-109508840-C-T
• rs146766120
• NM_020703.4:c.73G>A

Variant summary

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

The NM_020703.4(AMIGO1):​c.73G>A​(p.Ala25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,612,346 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (94 hom.)
• Consequence: AMIGO1 NM_020703.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460
• Publications: 3 publications found

Genes affected

AMIGO1 (HGNC:20824): (adhesion molecule with Ig like domain 1) Predicted to enable potassium channel regulator activity. Predicted to be involved in several processes, including heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; homophilic cell adhesion via plasma membrane adhesion molecules; and nervous system development. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in dendrite and neuronal cell body membrane. Predicted to be integral component of membrane. Predicted to colocalize with voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019631088).
• BP6: Variant 1-109508840-C-T is Benign according to our data. Variant chr1-109508840-C-T is described in ClinVar as Benign. ClinVar VariationId is 718581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00611 (929/152132) while in subpopulation SAS AF = 0.0439 (211/4804). AF 95% confidence interval is 0.0391. There are 12 homozygotes in GnomAd4. There are 486 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 929 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020703.4. 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
	AMIGO1	NM_020703.4	MANE Select	c.73G>A	p.Ala25Thr	missense	Exon 2 of 2	NP_065754.2	Q86WK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMIGO1	ENST00000369864.5	TSL:1 MANE Select	c.73G>A	p.Ala25Thr	missense	Exon 2 of 2	ENSP00000358880.4	Q86WK6
	AMIGO1	ENST00000369862.1	TSL:5	c.73G>A	p.Ala25Thr	missense	Exon 2 of 2	ENSP00000358878.1	Q86WK6
	AMIGO1	ENST00000887776.1		c.73G>A	p.Ala25Thr	missense	Exon 2 of 2	ENSP00000557835.1

Frequencies

GnomAD3 genomes AF: 0.00610 AC: 927 AN: 152014 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000776

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00647 AC: 1600 AN: 247174 AF XY: 0.00768

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.000728

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000538

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00291 AC: 4251 AN: 1460214 Hom.: 94 Cov.: 31 AF XY: 0.00386 AC XY: 2807 AN XY: 726300

African (AFR) AF: 0.0169 AC: 565 AN: 33456

American (AMR) AF: 0.000987 AC: 44 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39672

South Asian (SAS) AF: 0.0384 AC: 3306 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5758

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111158

Other (OTH) AF: 0.00428 AC: 258 AN: 60338

GnomAD4 genome AF: 0.00611 AC: 929 AN: 152132 Hom.: 12 Cov.: 32 AF XY: 0.00654 AC XY: 486 AN XY: 74364

African (AFR) AF: 0.0163 AC: 676 AN: 41508

American (AMR) AF: 0.00183 AC: 28 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000778 AC: 4 AN: 5140

South Asian (SAS) AF: 0.0439 AC: 211 AN: 4804

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00163 Hom.: 6

Bravo AF: 0.00565

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00759 AC: 921

Asia WGS AF: 0.0270 AC: 92 AN: 3476

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	0.090
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.046
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.040
Sift	Benign	0.96	T
Sift4G	Benign	0.81	T
Polyphen		0.043	B
Vest4		0.19
MVP		0.27
MPC		0.94
ClinPred		0.0079	T
GERP RS		4.1
Varity_R		0.057
gMVP		0.57
Mutation Taster		=95/5	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: rs146766120; hg19: chr1-110051462;