chr5-136163522-T-A

Variant names:

• chr5-136163522-T-A
• rs1109158
• NM_005903.7:c.775+131T>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-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 rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.775+131T>A		intron_variant	Intron 5 of 7	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.775+131T>A		intron_variant	Intron 5 of 7	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

African (AFR) AF: 0.524 AC: 5322 AN: 10152

American (AMR) AF: 0.276 AC: 2932 AN: 10630

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 4036 AN: 11806

East Asian (EAS) AF: 0.356 AC: 9049 AN: 25406

South Asian (SAS) AF: 0.185 AC: 4654 AN: 25198

European-Finnish (FIN) AF: 0.307 AC: 11158 AN: 36334

Middle Eastern (MID) AF: 0.318 AC: 598 AN: 1882

European-Non Finnish (NFE) AF: 0.280 AC: 87856 AN: 313532

Other (OTH) AF: 0.309 AC: 7527 AN: 24354

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

African (AFR) AF: 0.522 AC: 21611 AN: 41434

American (AMR) AF: 0.281 AC: 4298 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1946 AN: 5170

South Asian (SAS) AF: 0.185 AC: 892 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3184 AN: 10566

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.292 AC: 19825 AN: 67972

Other (OTH) AF: 0.384 AC: 811 AN: 2114

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
PhyloP100		0.10
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: rs1109158; hg19: chr5-135499211;