rs12116935

Positions:

• chr1-36323945-A-G

Variant summary

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

The ENST00000474766.1(SH3D21):​c.*1128A>G variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,222 control chromosomes in the GnomAD database, including 7,426 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 0.28 (7424 hom., cov: 33)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: SH3D21 ENST00000474766.1 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

Genes affected

SH3D21 (HGNC:26236): (SH3 domain containing 21) Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1B (HGNC:25558): (eva-1 homolog B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVA1B	NM_018166.3	c.-83T>C		5_prime_UTR_variant	1/3		NP_060636.1
SH3D21	XM_017002342.3	c.*2215A>G		3_prime_UTR_variant	17/17		XP_016857831.1
SH3D21	XM_017002340.2	c.2260+2167A>G		intron_variant			XP_016857829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3D21	ENST00000474766.1	c.*1128A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000500135
EVA1B	ENST00000270824.1	c.-83T>C		5_prime_UTR_variant	1/3	2		ENSP00000270824	P1
SH3D21	ENST00000505871.7	c.*2818A>G		3_prime_UTR_variant	13/13	2		ENSP00000421294

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43309 AN: 152088 Hom.: 7429 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.284 AC: 43296 AN: 152206 Hom.: 7424 Cov.: 33 AF XY: 0.284 AC XY: 21135 AN XY: 74410

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0694

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.318

Alfa AF: 0.373 Hom.: 17118

Bravo AF: 0.263

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs12116935; hg19: chr1-36789546;