rs17173769

Positions:

• chr7-151260343-T-C

Variant summary

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

The NM_003078.4(SMARCD3):​c.40-14672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,282 control chromosomes in the GnomAD database, including 165 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 0.031 (165 hom., cov: 32)
• Consequence: SMARCD3 NM_003078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

Genes affected

SMARCD3 (HGNC:11108): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD3	NM_001003802.2	c.40-14672A>G		intron_variant			NP_001003802.1
SMARCD3	NM_003078.4	c.40-14672A>G		intron_variant			NP_003069.2
SMARCD3	XM_047420758.1	c.-17+14771A>G		intron_variant			XP_047276714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCD3	ENST00000356800.6	c.40-14672A>G		intron_variant		1		ENSP00000349254.2
SMARCD3	ENST00000392811.6	c.40-14672A>G		intron_variant		1		ENSP00000376558.2
SMARCD3	ENST00000491651.1	c.40-14672A>G		intron_variant		4		ENSP00000419886.1
SMARCD3	ENST00000469154.5	n.70+14771A>G		intron_variant		5		ENSP00000417908.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4768 AN: 152162 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.00700

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0313 AC: 4768 AN: 152282 Hom.: 165 Cov.: 32 AF XY: 0.0326 AC XY: 2427 AN XY: 74460

Gnomad4 AFR AF: 0.00698

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0275

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0353 Hom.: 53

Bravo AF: 0.0379

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.90
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17173769; hg19: chr7-150957429;