rs6085297

Variant names:

• chr20-5862833-C-T
• rs6085297
• NM_152504.4:c.179-191C>T

Variant summary

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

The NM_152504.4(SHLD1):​c.179-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,184 control chromosomes in the GnomAD database, including 1,605 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 0.14 (1605 hom., cov: 33)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 4 publications found

Genes affected

SHLD1 (HGNC:26318): (shieldin complex subunit 1) Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in site of double-strand break. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHLD1	NM_152504.4	MANE Select	c.179-191C>T		intron	N/A	NP_689717.2
	SHLD1	NM_001303477.2		c.179-191C>T		intron	N/A	NP_001290406.1	Q8IYI0-1
	SHLD1	NM_001303478.2		c.83-191C>T		intron	N/A	NP_001290407.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHLD1	ENST00000303142.11	TSL:1 MANE Select	c.179-191C>T		intron	N/A	ENSP00000305875.6	Q8IYI0-1
	SHLD1	ENST00000875759.1		c.179-191C>T		intron	N/A	ENSP00000545818.1
	SHLD1	ENST00000915775.1		c.179-191C>T		intron	N/A	ENSP00000585834.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21052 AN: 152066 Hom.: 1606 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.138 AC: 21061 AN: 152184 Hom.: 1605 Cov.: 33 AF XY: 0.133 AC XY: 9885 AN XY: 74416

African (AFR) AF: 0.110 AC: 4587 AN: 41512

American (AMR) AF: 0.148 AC: 2258 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0959 AC: 462 AN: 4816

European-Finnish (FIN) AF: 0.101 AC: 1065 AN: 10592

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11795 AN: 68004

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.162 Hom.: 3603

Bravo AF: 0.141

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.29
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: rs6085297; hg19: chr20-5843479;