NM_020350.5:c.27+4186T>G

Variant names:

• chr1-11740421-T-G
• rs11121816
• NM_020350.5:c.27+4186T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020350.5(AGTRAP):​c.27+4186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,112 control chromosomes in the GnomAD database, including 11,162 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 0.38 (11162 hom., cov: 33)
• Consequence: AGTRAP NM_020350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 8 publications found

Genes affected

AGTRAP (HGNC:13539): (angiotensin II receptor associated protein) This gene encodes a transmembrane protein localized to the plasma membrane and perinuclear vesicular structures. The gene product interacts with the angiotensin II type I receptor and negatively regulates angiotensin II signaling. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020350.5. 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
	AGTRAP	NM_020350.5	MANE Select	c.27+4186T>G		intron	N/A	NP_065083.3
	AGTRAP	NM_001040196.2		c.27+4186T>G		intron	N/A	NP_001035286.1
	AGTRAP	NM_001040194.2		c.27+4186T>G		intron	N/A	NP_001035284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTRAP	ENST00000314340.10	TSL:1 MANE Select	c.27+4186T>G		intron	N/A	ENSP00000319713.5
	AGTRAP	ENST00000376629.8	TSL:1	c.27+4186T>G		intron	N/A	ENSP00000365816.4
	AGTRAP	ENST00000376627.6	TSL:5	c.28-4112T>G		intron	N/A	ENSP00000365814.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57655 AN: 151994 Hom.: 11160 Cov.: 33

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57692 AN: 152112 Hom.: 11162 Cov.: 33 AF XY: 0.382 AC XY: 28411 AN XY: 74372

African (AFR) AF: 0.361 AC: 14984 AN: 41488

American (AMR) AF: 0.458 AC: 6995 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2939 AN: 5180

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3426 AN: 10574

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24960 AN: 67976

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.350 Hom.: 4086

Bravo AF: 0.391

Asia WGS AF: 0.428 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.34
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: rs11121816; hg19: chr1-11800478;