chr5-136182554-G-T

Position:

• chr5-136182554-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000545279.6(SMAD5):​c.*5074G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,478 control chromosomes in the GnomAD database, including 10,886 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 (10864 hom., cov: 33)
  • Exomes 𝑓: 0.31 (22 hom.)
• Consequence: SMAD5 ENST00000545279.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• 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/exons	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.*5074G>T		3_prime_UTR_variant	8/8	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.*5074G>T		3_prime_UTR_variant	8/8	1	NM_005903.7	ENSP00000441954	P1
SMAD5	ENST00000545620.5	c.*5074G>T		3_prime_UTR_variant	7/7	5		ENSP00000446474	P1
SMAD5	ENST00000513418.1	c.165-4607G>T		intron_variant, NMD_transcript_variant		5		ENSP00000427650

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54751 AN: 151928 Hom.: 10835 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.315 AC: 136 AN: 432 Hom.: 22 Cov.: 0 AF XY: 0.338 AC XY: 88 AN XY: 260

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.361 AC: 54826 AN: 152046 Hom.: 10864 Cov.: 33 AF XY: 0.356 AC XY: 26485 AN XY: 74332

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.385

Alfa AF: 0.265 Hom.: 1563

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.70

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: rs7031; hg19: chr5-135518242; COSMIC: COSV72843585; COSMIC: COSV72843585;