chr8-12183621-C-T

Variant names:

• chr8-12183621-C-T
• rs1477357507
• NM_001083537.4:c.876G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001083537.4(FAM86B1):​c.876G>A​(p.Leu292Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000065 (0 hom., cov: 13)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229
• Publications: 1 publications found

Genes affected

FAM86B1 (HGNC:28268): (family with sequence similarity 86 member B1) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. [provided by Alliance of Genome Resources, Apr 2022]

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-12183621-C-T is Benign according to our data. Variant chr8-12183621-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.229 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083537.4. 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
	FAM86B1	NM_001083537.4	MANE Select	c.876G>A	p.Leu292Leu	synonymous	Exon 7 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.673G>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B1	ENST00000448228.7	TSL:5 MANE Select	c.876G>A	p.Leu292Leu	synonymous	Exon 7 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*568G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*568G>A		3_prime_UTR	Exon 5 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes AF: 0.0000655 AC: 7 AN: 106896 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000974

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000675 AC: 6 AN: 88838 AF XY: 0.0000877

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000850

Gnomad OTH exome AF: 0.000376

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000105 AC: 68 AN: 645026 Hom.: 0 Cov.: 8 AF XY: 0.000123 AC XY: 42 AN XY: 341336

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18758

American (AMR) AF: 0.0000296 AC: 1 AN: 33780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18872

East Asian (EAS) AF: 0.0000313 AC: 1 AN: 31932

South Asian (SAS) AF: 0.0000469 AC: 3 AN: 63994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2446

European-Non Finnish (NFE) AF: 0.000149 AC: 59 AN: 394710

Other (OTH) AF: 0.000123 AC: 4 AN: 32440

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000654 AC: 7 AN: 107002 Hom.: 0 Cov.: 13 AF XY: 0.0000596 AC XY: 3 AN XY: 50332

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000352 AC: 1 AN: 28372

American (AMR) AF: 0.000107 AC: 1 AN: 9360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.00 AC: 0 AN: 3728

South Asian (SAS) AF: 0.00 AC: 0 AN: 2576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000975 AC: 5 AN: 51308

Other (OTH) AF: 0.00 AC: 0 AN: 1248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000127868), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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: rs1477357507; hg19: chr8-12041130;