chr1-235993977-T-G

Variant names:

• chr1-235993977-T-G
• rs16833075
• NM_002508.3:c.2528-105A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002508.3. 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
	NID1	NM_002508.3	MANE Select	c.2528-105A>C		intron	N/A	NP_002499.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NID1	ENST00000264187.7	TSL:1 MANE Select	c.2528-105A>C		intron	N/A	ENSP00000264187.6
	NID1	ENST00000366595.7	TSL:1	c.2129-105A>C		intron	N/A	ENSP00000355554.3

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

African (AFR) AF: 0.189 AC: 3513 AN: 18552

American (AMR) AF: 0.217 AC: 4686 AN: 21554

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 2139 AN: 16180

East Asian (EAS) AF: 0.584 AC: 18825 AN: 32236

South Asian (SAS) AF: 0.327 AC: 17882 AN: 54690

European-Finnish (FIN) AF: 0.137 AC: 5085 AN: 37182

Middle Eastern (MID) AF: 0.178 AC: 752 AN: 4236

European-Non Finnish (NFE) AF: 0.174 AC: 95490 AN: 549560

Other (OTH) AF: 0.215 AC: 7897 AN: 36670

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

African (AFR) AF: 0.196 AC: 8129 AN: 41532

American (AMR) AF: 0.200 AC: 3053 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2905 AN: 5162

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1498 AN: 10610

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11633 AN: 68010

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.184 Hom.: 8744

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		0.090
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: rs16833075; hg19: chr1-236157277; COSMIC: COSV51616658;