rs16833075

Positions:

• chr1-235993977-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002508.3(NID1):​c.2528-105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 923,086 control chromosomes in the GnomAD database, including 23,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3453 hom., cov: 33)
  • Exomes 𝑓: 0.20 (20018 hom.)
• Consequence: NID1 NM_002508.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0900

Genes affected

NID1 (HGNC:7821): (nidogen 1) This gene encodes a member of the nidogen family of basement membrane glycoproteins. The protein interacts with several other components of basement membranes, and may play a role in cell interactions with the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-235993977-T-G is Benign according to our data. Variant chr1-235993977-T-G is described in ClinVar as [Benign]. Clinvar id is 1282638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NID1	NM_002508.3	c.2528-105A>C		intron_variant		ENST00000264187.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NID1	ENST00000264187.7	c.2528-105A>C		intron_variant		1	NM_002508.3	P1
NID1	ENST00000366595.7	c.2129-105A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29970 AN: 152108 Hom.: 3452 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.203 AC: 156269 AN: 770860 Hom.: 20018 AF XY: 0.207 AC XY: 80529 AN XY: 388758

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.197 AC: 29981 AN: 152226 Hom.: 3453 Cov.: 33 AF XY: 0.198 AC XY: 14773 AN XY: 74446

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.208

Alfa AF: 0.179 Hom.: 5183

Bravo AF: 0.201

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs16833075; hg19: chr1-236157277; COSMIC: COSV51616658;