rs80136550

Variant names:

• chr5-157459885-C-T
• rs80136550
• ENST00000519499.2:c.-2233+123G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000519499.2(ENSG00000285868):​c.-2233+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 398,866 control chromosomes in the GnomAD database, including 1,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (613 hom., cov: 32)
  • Exomes 𝑓: 0.092 (1164 hom.)
• Consequence: ENSG00000285868 ENST00000519499.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163
• Publications: 1 publications found

Genes affected

ENSG00000285868 (HGNC:):

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

NIPAL4-DT (HGNC:55542): (NIPAL4 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-157459885-C-T is Benign according to our data. Variant chr5-157459885-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267802.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519499.2. 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
	NIPAL4-DT	NR_136204.1		n.93+123G>A		intron	N/A
	NIPAL4-DT	NR_136205.1		n.93+123G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2233+123G>A		intron	N/A	ENSP00000496943.1
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28380G>A		intron	N/A	ENSP00000428376.1	E5RIS2

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12026 AN: 152142 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0799

GnomAD4 exome AF: 0.0923 AC: 22759 AN: 246606 Hom.: 1164 AF XY: 0.0932 AC XY: 11656 AN XY: 125028

African (AFR) AF: 0.0325 AC: 225 AN: 6914

American (AMR) AF: 0.0715 AC: 538 AN: 7524

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 984 AN: 9114

East Asian (EAS) AF: 0.0369 AC: 817 AN: 22168

South Asian (SAS) AF: 0.192 AC: 687 AN: 3582

European-Finnish (FIN) AF: 0.0935 AC: 1932 AN: 20656

Middle Eastern (MID) AF: 0.103 AC: 134 AN: 1300

European-Non Finnish (NFE) AF: 0.100 AC: 15954 AN: 158912

Other (OTH) AF: 0.0905 AC: 1488 AN: 16436

GnomAD4 genome AF: 0.0791 AC: 12040 AN: 152260 Hom.: 613 Cov.: 32 AF XY: 0.0808 AC XY: 6011 AN XY: 74436

African (AFR) AF: 0.0299 AC: 1244 AN: 41562

American (AMR) AF: 0.0786 AC: 1203 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.0270 AC: 140 AN: 5178

South Asian (SAS) AF: 0.192 AC: 926 AN: 4820

European-Finnish (FIN) AF: 0.0966 AC: 1025 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6817 AN: 68002

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0779 Hom.: 75

Bravo AF: 0.0740

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.51
PhyloP100		-0.16
PromoterAI		-0.044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs80136550; hg19: chr5-156886893;