rs1109158

Positions:

• chr5-136163522-T-A
• chr5-136163522-T-G

Variant summary

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

The NM_005903.7(SMAD5):​c.775+131T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 611,336 control chromosomes in the GnomAD database, including 31,128 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 (10442 hom., cov: 32)
  • Exomes 𝑓: 0.29 (20686 hom.)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.775+131T>A		intron_variant		ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.775+131T>A		intron_variant		1	NM_005903.7	ENSP00000441954.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53965 AN: 151924 Hom.: 10420 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.290 AC: 133132 AN: 459294 Hom.: 20686 AF XY: 0.287 AC XY: 67336 AN XY: 235026

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.355 AC: 54031 AN: 152042 Hom.: 10442 Cov.: 32 AF XY: 0.351 AC XY: 26100 AN XY: 74320

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.384

Alfa AF: 0.315 Hom.: 1029

Bravo AF: 0.368

Asia WGS AF: 0.340 AC: 1186 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.43

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: rs1109158; hg19: chr5-135499211;