5-50441119-C-G

Variant names:

• chr5-50441119-C-G
• rs1028444021
• NM_198449.3:c.33G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198449.3(EMB):​c.33G>C​(p.Arg11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,511,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: EMB NM_198449.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.369
• Publications: 0 publications found

Genes affected

EMB (HGNC:30465): (embigin) This gene encodes a transmembrane glycoprotein that is a member of the immunoglobulin superfamily. The encoded protein may be involved in cell growth and development by mediating interactions between the cell and extracellular matrix. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Jan 2009]

ENSG00000298748 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060700864).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198449.3. 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
	EMB	NM_198449.3	MANE Select	c.33G>C	p.Arg11Ser	missense	Exon 1 of 9	NP_940851.1	Q6PCB8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMB	ENST00000303221.10	TSL:1 MANE Select	c.33G>C	p.Arg11Ser	missense	Exon 1 of 9	ENSP00000302289.5	Q6PCB8-1
	EMB	ENST00000872546.1		c.33G>C	p.Arg11Ser	missense	Exon 1 of 8	ENSP00000542605.1
	EMB	ENST00000508934.5	TSL:5	c.33G>C	p.Arg11Ser	missense	Exon 1 of 9	ENSP00000425215.1	D6RDX7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152128 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000263 AC: 3 AN: 113986 AF XY: 0.0000478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000699

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 165 AN: 1359788 Hom.: 0 Cov.: 31 AF XY: 0.000101 AC XY: 68 AN XY: 670356

African (AFR) AF: 0.00 AC: 0 AN: 28898

American (AMR) AF: 0.00 AC: 0 AN: 33536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24478

East Asian (EAS) AF: 0.00 AC: 0 AN: 33448

South Asian (SAS) AF: 0.00 AC: 0 AN: 76044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36476

Middle Eastern (MID) AF: 0.000239 AC: 1 AN: 4188

European-Non Finnish (NFE) AF: 0.000152 AC: 162 AN: 1066056

Other (OTH) AF: 0.0000353 AC: 2 AN: 56664

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152128 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000384 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.5
DANN	Benign	0.78
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.37
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.013
Sift	Benign	0.33	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.29		Loss of methylation at R11 (P = 0.0159)
MVP		0.31
MPC		0.11
ClinPred		0.040	T
GERP RS		-0.15
PromoterAI		0.085	Neutral
Varity_R		0.079
gMVP		0.55
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1028444021; hg19: chr5-49736953;