rs1105282

Variant names:

• chr5-157460125-A-G
• rs1105282
• ENST00000517951.5:n.*1741+28140T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-157460125-A-G
• chr5-157460125-A-C
• chr5-157460125-A-T

Variant summary

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

The ENST00000517951.5(ADAM19):​n.*1741+28140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,410,364 control chromosomes in the GnomAD database, including 90,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11148 hom., cov: 33)
  • Exomes 𝑓: 0.35 (79010 hom.)
• Consequence: ADAM19 ENST00000517951.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.658
• Publications: 18 publications found

Genes affected

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 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

ENSG00000285868 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-157460125-A-G is Benign according to our data. Variant chr5-157460125-A-G is described in ClinVar as Benign. ClinVar VariationId is 257433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517951.5. 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
	NIPAL4	NM_001099287.2	MANE Select	c.-196A>G		upstream_gene	N/A	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.-196A>G		upstream_gene	N/A	NP_001165763.2	Q0D2K0-2
	NIPAL4-DT	NR_136204.1		n.-25T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28140T>C		intron	N/A	ENSP00000428376.1	E5RIS2
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-196A>G		upstream_gene	N/A	ENSP00000311687.8	Q0D2K0-1
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2350T>C		upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57139 AN: 151908 Hom.: 11131 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.368 AC: 17039 AN: 46260 AF XY: 0.371

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.711

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.348 AC: 438407 AN: 1258338 Hom.: 79010 Cov.: 28 AF XY: 0.348 AC XY: 212080 AN XY: 609606

African (AFR) AF: 0.385 AC: 9309 AN: 24156

American (AMR) AF: 0.317 AC: 5027 AN: 15840

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 6312 AN: 17434

East Asian (EAS) AF: 0.671 AC: 20396 AN: 30412

South Asian (SAS) AF: 0.348 AC: 20534 AN: 58996

European-Finnish (FIN) AF: 0.345 AC: 15202 AN: 44118

Middle Eastern (MID) AF: 0.376 AC: 1468 AN: 3902

European-Non Finnish (NFE) AF: 0.338 AC: 341534 AN: 1011910

Other (OTH) AF: 0.361 AC: 18625 AN: 51570

GnomAD4 genome AF: 0.376 AC: 57188 AN: 152026 Hom.: 11148 Cov.: 33 AF XY: 0.379 AC XY: 28202 AN XY: 74318

African (AFR) AF: 0.392 AC: 16255 AN: 41508

American (AMR) AF: 0.360 AC: 5510 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3698 AN: 5136

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4824

European-Finnish (FIN) AF: 0.346 AC: 3657 AN: 10584

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23762 AN: 67892

Other (OTH) AF: 0.374 AC: 790 AN: 2114

Alfa AF: 0.363 Hom.: 1591

Bravo AF: 0.373

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Autosomal recessive congenital ichthyosis 6 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.66
PromoterAI		-0.45	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: rs1105282; hg19: chr5-156887133; COSMIC: COSV100357189; COSMIC: COSV100357189;