chr10-80617834-T-C

Variant names:

• chr10-80617834-T-C
• rs6586111
• NM_001388272.1:c.988+8283T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388272.1(SH2D4B):​c.988+8283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,062 control chromosomes in the GnomAD database, including 22,135 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 0.52 (22135 hom., cov: 32)
• Consequence: SH2D4B NM_001388272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 7 publications found

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4B	NM_001388272.1	MANE Select	c.988+8283T>C		intron	N/A	NP_001375201.1
	SH2D4B	NM_207372.2		c.985+8283T>C		intron	N/A	NP_997255.2
	SH2D4B	NM_001145719.1		c.841+8283T>C		intron	N/A	NP_001139191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4B	ENST00000646907.2	MANE Select	c.988+8283T>C		intron	N/A	ENSP00000494732.1
	SH2D4B	ENST00000339284.6	TSL:2	c.985+8283T>C		intron	N/A	ENSP00000345295.2
	SH2D4B	ENST00000313455.5	TSL:2	c.841+8283T>C		intron	N/A	ENSP00000314242.4

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79537 AN: 151944 Hom.: 22092 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.524 AC: 79633 AN: 152062 Hom.: 22135 Cov.: 32 AF XY: 0.524 AC XY: 38918 AN XY: 74328

African (AFR) AF: 0.690 AC: 28634 AN: 41474

American (AMR) AF: 0.588 AC: 8976 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3802 AN: 5178

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4814

European-Finnish (FIN) AF: 0.404 AC: 4277 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29181 AN: 67958

Other (OTH) AF: 0.524 AC: 1107 AN: 2112

Alfa AF: 0.479 Hom.: 31425

Bravo AF: 0.549

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.79
PhyloP100		-0.15
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: rs6586111; hg19: chr10-82377590;