rs13179769

Variant names:

• chr5-136158171-C-A
• rs13179769
• NM_005903.7:c.404-2685C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-136158171-C-A
• chr5-136158171-C-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.404-2685C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,736 control chromosomes in the GnomAD database, including 10,837 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 (10837 hom., cov: 31)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.404-2685C>A		intron_variant	Intron 3 of 7	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.404-2685C>A		intron_variant	Intron 3 of 7	1	NM_005903.7	ENSP00000441954.2
SMAD5	ENST00000509297.6	c.404-2685C>A		intron_variant	Intron 3 of 7	1		ENSP00000426696.2
SMAD5	ENST00000545620.5	c.404-2685C>A		intron_variant	Intron 2 of 6	5		ENSP00000446474.2
SMAD5	ENST00000514777.1	n.60-14263C>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54639 AN: 151618 Hom.: 10808 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.362

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: 0.361 AC: 54714 AN: 151736 Hom.: 10837 Cov.: 31 AF XY: 0.356 AC XY: 26418 AN XY: 74152

African (AFR) AF: 0.539 AC: 22283 AN: 41364

American (AMR) AF: 0.285 AC: 4342 AN: 15252

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

East Asian (EAS) AF: 0.376 AC: 1934 AN: 5146

South Asian (SAS) AF: 0.185 AC: 888 AN: 4810

European-Finnish (FIN) AF: 0.302 AC: 3174 AN: 10494

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.292 AC: 19820 AN: 67896

Other (OTH) AF: 0.384 AC: 809 AN: 2106

Alfa AF: 0.334 Hom.: 1559

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.54
PhyloP100		-2.4
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: rs13179769; hg19: chr5-135493860;