X-129654737-A-G

Variant names:

• chrX-129654737-A-G
• rs2281069
• NM_017413.5:c.-107T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017413.5(APLN):​c.-107T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 509,770 control chromosomes in the GnomAD database, including 3,124 homozygotes. There are 12,289 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1535 hom., 4505 hem., cov: 24)
  • Exomes 𝑓: 0.079 (1589 hom. 7784 hem.)
• Consequence: APLN NM_017413.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04
• Publications: 1 publications found

Genes affected

APLN (HGNC:16665): (apelin) This gene encodes a peptide that functions as an endogenous ligand for the G-protein coupled apelin receptor. The encoded preproprotein is proteolytically processed into biologically active C-terminal peptide fragments. These peptide fragments activate different tissue specific signaling pathways that regulate diverse biological functions including fluid homeostasis, cardiovascular function and insulin secretion. This protein also functions as a coreceptor for the human immunodeficiency virus 1. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-129654737-A-G is Benign according to our data. Variant chrX-129654737-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017413.5. 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
	APLN	NM_017413.5	MANE Select	c.-107T>C		5_prime_UTR	Exon 1 of 3	NP_059109.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.-107T>C		5_prime_UTR	Exon 1 of 3	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.-107T>C		5_prime_UTR	Exon 1 of 3	ENSP00000535599.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15977 AN: 111412 Hom.: 1532 Cov.: 24

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0549

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.0788 AC: 31396 AN: 398313 Hom.: 1589 Cov.: 6 AF XY: 0.104 AC XY: 7784 AN XY: 74531

African (AFR) AF: 0.363 AC: 3310 AN: 9118

American (AMR) AF: 0.0941 AC: 431 AN: 4581

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 428 AN: 6540

East Asian (EAS) AF: 0.316 AC: 4686 AN: 14830

South Asian (SAS) AF: 0.143 AC: 1113 AN: 7775

European-Finnish (FIN) AF: 0.0461 AC: 723 AN: 15670

Middle Eastern (MID) AF: 0.0624 AC: 69 AN: 1105

European-Non Finnish (NFE) AF: 0.0583 AC: 18682 AN: 320564

Other (OTH) AF: 0.108 AC: 1954 AN: 18130

GnomAD4 genome AF: 0.143 AC: 15994 AN: 111457 Hom.: 1535 Cov.: 24 AF XY: 0.133 AC XY: 4505 AN XY: 33915

African (AFR) AF: 0.331 AC: 10152 AN: 30644

American (AMR) AF: 0.0997 AC: 1075 AN: 10787

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 196 AN: 2636

East Asian (EAS) AF: 0.317 AC: 1079 AN: 3407

South Asian (SAS) AF: 0.120 AC: 333 AN: 2782

European-Finnish (FIN) AF: 0.0462 AC: 280 AN: 6055

Middle Eastern (MID) AF: 0.0558 AC: 12 AN: 215

European-Non Finnish (NFE) AF: 0.0503 AC: 2651 AN: 52726

Other (OTH) AF: 0.141 AC: 216 AN: 1530

Alfa AF: 0.0163 Hom.: 84

Bravo AF: 0.161

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.57
PhyloP100		-2.0
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	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: rs2281069; hg19: chrX-128788714;