rs1049607

Variant names:

• chr1-209615358-T-C
• rs1049607
• NM_000228.3:c.3432A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-209615358-T-C
• chr1-209615358-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000228.3(LAMB3):​c.3432A>G​(p.Ser1144Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,612,508 control chromosomes in the GnomAD database, including 118,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15536 hom., cov: 33)
  • Exomes 𝑓: 0.37 (103158 hom.)
• Consequence: LAMB3 NM_000228.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -4.67
• Publications: 16 publications found

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

LAMB3 Gene-Disease associations (from GenCC):

• junctional epidermolysis bullosa

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• junctional epidermolysis bullosa Herlitz type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics
• amelogenesis imperfecta type 1A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized junctional epidermolysis bullosa non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-209615358-T-C is Benign according to our data. Variant chr1-209615358-T-C is described in ClinVar as Benign. ClinVar VariationId is 255595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000228.3. 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
	LAMB3	NM_000228.3	MANE Select	c.3432A>G	p.Ser1144Ser	synonymous	Exon 23 of 23	NP_000219.2	A0A0S2Z3R6
	LAMB3	NM_001017402.2		c.3432A>G	p.Ser1144Ser	synonymous	Exon 22 of 22	NP_001017402.1	Q13751
	LAMB3	NM_001127641.1		c.3432A>G	p.Ser1144Ser	synonymous	Exon 23 of 23	NP_001121113.1	A0A0S2Z3R6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB3	ENST00000356082.9	TSL:1 MANE Select	c.3432A>G	p.Ser1144Ser	synonymous	Exon 23 of 23	ENSP00000348384.3	Q13751
	LAMB3	ENST00000367030.7	TSL:1	c.3432A>G	p.Ser1144Ser	synonymous	Exon 23 of 23	ENSP00000355997.3	Q13751
	LAMB3	ENST00000391911.5	TSL:1	c.3432A>G	p.Ser1144Ser	synonymous	Exon 22 of 22	ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66644 AN: 151998 Hom.: 15520 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.394 AC: 98338 AN: 249352 AF XY: 0.390

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.416

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.373 AC: 544006 AN: 1460392 Hom.: 103158 Cov.: 38 AF XY: 0.373 AC XY: 270932 AN XY: 726446

African (AFR) AF: 0.618 AC: 20656 AN: 33430

American (AMR) AF: 0.376 AC: 16811 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 10988 AN: 26094

East Asian (EAS) AF: 0.415 AC: 16439 AN: 39634

South Asian (SAS) AF: 0.401 AC: 34580 AN: 86134

European-Finnish (FIN) AF: 0.386 AC: 20527 AN: 53130

Middle Eastern (MID) AF: 0.338 AC: 1945 AN: 5758

European-Non Finnish (NFE) AF: 0.359 AC: 399004 AN: 1111198

Other (OTH) AF: 0.382 AC: 23056 AN: 60350

GnomAD4 genome AF: 0.439 AC: 66704 AN: 152116 Hom.: 15536 Cov.: 33 AF XY: 0.437 AC XY: 32518 AN XY: 74374

African (AFR) AF: 0.611 AC: 25334 AN: 41484

American (AMR) AF: 0.389 AC: 5945 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2110 AN: 5166

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4822

European-Finnish (FIN) AF: 0.404 AC: 4279 AN: 10586

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24437 AN: 67972

Other (OTH) AF: 0.419 AC: 887 AN: 2116

Alfa AF: 0.391 Hom.: 11628

Bravo AF: 0.443

Asia WGS AF: 0.406 AC: 1416 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Amelogenesis imperfecta type 1A (1)
-	-	1	Junctional epidermolysis bullosa (1)
-	-	1	Junctional epidermolysis bullosa gravis of Herlitz (1)
-	-	1	Junctional epidermolysis bullosa, non-Herlitz type (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.035
DANN	Benign	0.59
PhyloP100		-4.7
Mutation Taster		=97/3	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: rs1049607; hg19: chr1-209788703; COSMIC: COSV50520600; COSMIC: COSV50520600;