2-218265791-G-A

Variant names:

• chr2-218265791-G-A
• rs1079204
• NM_001087.5:c.879+40C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001087.5(AAMP):​c.879+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,589,694 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (79 hom., cov: 32)
  • Exomes 𝑓: 0.029 (733 hom.)
• Consequence: AAMP NM_001087.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743
• Publications: 11 publications found

Genes affected

AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0312 (4758/152286) while in subpopulation AFR AF = 0.0346 (1436/41548). AF 95% confidence interval is 0.0331. There are 79 homozygotes in GnomAd4. There are 2295 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001087.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAMP	NM_001087.5	MANE Select	c.879+40C>T		intron	N/A	NP_001078.2
	AAMP	NM_001302545.2		c.882+40C>T		intron	N/A	NP_001289474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAMP	ENST00000248450.9	TSL:1 MANE Select	c.879+40C>T		intron	N/A	ENSP00000248450.4
	AAMP	ENST00000444053.5	TSL:1	c.882+40C>T		intron	N/A	ENSP00000403343.1
	AAMP	ENST00000465442.1	TSL:2	n.642C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4756 AN: 152168 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0349

GnomAD2 exomes AF: 0.0267 AC: 6540 AN: 244588 AF XY: 0.0268

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.0218

Gnomad ASJ exome AF: 0.0507

Gnomad EAS exome AF: 0.00252

Gnomad FIN exome AF: 0.0225

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0295 AC: 42335 AN: 1437408 Hom.: 733 Cov.: 29 AF XY: 0.0294 AC XY: 21001 AN XY: 715168

African (AFR) AF: 0.0330 AC: 1089 AN: 33016

American (AMR) AF: 0.0226 AC: 1004 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 1251 AN: 25736

East Asian (EAS) AF: 0.00132 AC: 52 AN: 39432

South Asian (SAS) AF: 0.0169 AC: 1447 AN: 85486

European-Finnish (FIN) AF: 0.0231 AC: 1186 AN: 51410

Middle Eastern (MID) AF: 0.0407 AC: 233 AN: 5720

European-Non Finnish (NFE) AF: 0.0315 AC: 34379 AN: 1092654

Other (OTH) AF: 0.0284 AC: 1694 AN: 59552

GnomAD4 genome AF: 0.0312 AC: 4758 AN: 152286 Hom.: 79 Cov.: 32 AF XY: 0.0308 AC XY: 2295 AN XY: 74454

African (AFR) AF: 0.0346 AC: 1436 AN: 41548

American (AMR) AF: 0.0246 AC: 377 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5182

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4822

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2260 AN: 68024

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0305 Hom.: 81

Bravo AF: 0.0317

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.010
DANN	Benign	0.60
PhyloP100		-0.74
PromoterAI		-0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1079204; hg19: chr2-219130514;