rs13166063

Variant names:

• chr5-136158385-T-C
• rs13166063
• NM_005903.7:c.404-2471T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-136158385-T-C
• chr5-136158385-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005903.7(SMAD5):​c.404-2471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,036 control chromosomes in the GnomAD database, including 10,576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10576 hom., cov: 32)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 7 publications found

Genes affected

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005903.7. 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
	SMAD5	NM_005903.7	MANE Select	c.404-2471T>C		intron	N/A	NP_005894.3
	SMAD5	NM_001001419.3		c.404-2471T>C		intron	N/A	NP_001001419.1	Q99717
	SMAD5	NM_001001420.3		c.404-2471T>C		intron	N/A	NP_001001420.1	Q99717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD5	ENST00000545279.6	TSL:1 MANE Select	c.404-2471T>C		intron	N/A	ENSP00000441954.2	Q99717
	SMAD5	ENST00000509297.6	TSL:1	c.404-2471T>C		intron	N/A	ENSP00000426696.2	Q99717
	SMAD5	ENST00000545620.5	TSL:5	c.404-2471T>C		intron	N/A	ENSP00000446474.2	Q99717

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54194 AN: 151918 Hom.: 10548 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 54267 AN: 152036 Hom.: 10576 Cov.: 32 AF XY: 0.353 AC XY: 26197 AN XY: 74308

African (AFR) AF: 0.527 AC: 21858 AN: 41454

American (AMR) AF: 0.282 AC: 4312 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1935 AN: 5160

South Asian (SAS) AF: 0.184 AC: 890 AN: 4826

European-Finnish (FIN) AF: 0.300 AC: 3167 AN: 10546

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19828 AN: 67978

Other (OTH) AF: 0.384 AC: 812 AN: 2114

Alfa AF: 0.320 Hom.: 10525

Bravo AF: 0.370

Asia WGS AF: 0.341 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		0.25
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: rs13166063; hg19: chr5-135494074;