1-235978953-T-G

Position:

• chr1-235978953-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.3622+42A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,382,254 control chromosomes in the GnomAD database, including 36,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5482 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31299 hom.)
• Consequence: NID1 NM_002508.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490

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=-0.95).
• BP6: Variant 1-235978953-T-G is Benign according to our data. Variant chr1-235978953-T-G is described in ClinVar as [Benign]. Clinvar id is 1242420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NID1	NM_002508.3	c.3622+42A>C		intron_variant		ENST00000264187.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NID1	ENST00000264187.7	c.3622+42A>C		intron_variant		1	NM_002508.3	P1
NID1	ENST00000366595.7	c.3223+42A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37222 AN: 151912 Hom.: 5478 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.236 AC: 58277 AN: 247030 Hom.: 8642 AF XY: 0.230 AC XY: 30738 AN XY: 133510

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.605

Gnomad SAS exome AF: 0.253

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.207 AC: 255181 AN: 1230224 Hom.: 31299 Cov.: 17 AF XY: 0.208 AC XY: 129433 AN XY: 622512

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.634

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.245 AC: 37247 AN: 152030 Hom.: 5482 Cov.: 32 AF XY: 0.245 AC XY: 18213 AN XY: 74316

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.250

Alfa AF: 0.200 Hom.: 743

Bravo AF: 0.258

Asia WGS AF: 0.397 AC: 1381 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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.63

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: rs12032474; hg19: chr1-236142253;