rs470358

Variant names:

• chr11-102797971-T-C
• rs470358
• NM_002421.4:c.105+17A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-102797971-T-C
• chr11-102797971-T-A

Variant summary

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

The NM_002421.4(MMP1):​c.105+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,545,902 control chromosomes in the GnomAD database, including 288,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33408 hom., cov: 32)
  • Exomes 𝑓: 0.60 (255473 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0610
• Publications: 28 publications found

Genes affected

MMP1 (HGNC:7155): (matrix metallopeptidase 1) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

WTAPP1 (HGNC:):

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-102797971-T-C is Benign according to our data. Variant chr11-102797971-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002421.4. 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
	MMP1	NM_002421.4	MANE Select	c.105+17A>G		intron	N/A	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.-53+128A>G		intron	N/A	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.584-53T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.105+17A>G		intron	N/A	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.325-53T>C		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.584-53T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99685 AN: 151992 Hom.: 33379 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.602 AC: 145180 AN: 240986 AF XY: 0.599

Gnomad AFR exome AF: 0.812

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.650

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.603 AC: 840613 AN: 1393792 Hom.: 255473 Cov.: 21 AF XY: 0.602 AC XY: 419120 AN XY: 696696

African (AFR) AF: 0.823 AC: 26110 AN: 31724

American (AMR) AF: 0.542 AC: 22950 AN: 42350

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16344 AN: 25260

East Asian (EAS) AF: 0.611 AC: 24025 AN: 39310

South Asian (SAS) AF: 0.564 AC: 46788 AN: 82924

European-Finnish (FIN) AF: 0.613 AC: 32274 AN: 52656

Middle Eastern (MID) AF: 0.617 AC: 3480 AN: 5644

European-Non Finnish (NFE) AF: 0.600 AC: 633390 AN: 1055846

Other (OTH) AF: 0.607 AC: 35252 AN: 58078

GnomAD4 genome AF: 0.656 AC: 99766 AN: 152110 Hom.: 33408 Cov.: 32 AF XY: 0.652 AC XY: 48509 AN XY: 74358

African (AFR) AF: 0.808 AC: 33548 AN: 41498

American (AMR) AF: 0.574 AC: 8768 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2267 AN: 3464

East Asian (EAS) AF: 0.563 AC: 2916 AN: 5178

South Asian (SAS) AF: 0.584 AC: 2816 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6378 AN: 10578

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40942 AN: 67978

Other (OTH) AF: 0.639 AC: 1351 AN: 2114

Alfa AF: 0.614 Hom.: 34862

Bravo AF: 0.661

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		-0.061
PromoterAI		0.085	Neutral
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: rs470358; hg19: chr11-102668702; COSMIC: COSV59510658;