rs13166063

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000545279.6(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 ENST00000545279.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.404-2471T>C		intron_variant		ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.404-2471T>C		intron_variant		1	NM_005903.7	ENSP00000441954	P1
SMAD5	ENST00000509297.6	c.404-2471T>C		intron_variant		1		ENSP00000426696	P1
SMAD5	ENST00000545620.5	c.404-2471T>C		intron_variant		5		ENSP00000446474	P1
SMAD5	ENST00000514777.1	n.60-14049T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.384

Alfa AF: 0.311 Hom.: 7447

Bravo AF: 0.370

Asia WGS AF: 0.341 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs13166063; hg19: chr5-135494074;