rs376073852

Variant names:

• chr8-12185414-C-T
• rs376073852
• NM_001083537.4:c.752G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-12185414-C-T
• chr8-12185414-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001083537.4(FAM86B1):​c.752G>A​(p.Arg251His) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 148,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00011 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM86B1 NM_001083537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.752G>A	p.Arg251His	missense	Exon 6 of 7	NP_001077006.1	Q8N7N1-2
	FAM86B1	NR_003494.3		n.549G>A		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM86B1	ENST00000448228.7	TSL:5 MANE Select	c.752G>A	p.Arg251His	missense	Exon 6 of 7	ENSP00000407067.2	Q8N7N1-2
	FAM86B1	ENST00000524893.5	TSL:1	n.*302G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000436024.1	E9PLW5
	FAM86B1	ENST00000524893.5	TSL:1	n.*302G>A		3_prime_UTR	Exon 4 of 5	ENSP00000436024.1	E9PLW5

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 23 AN: 148262 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000148 AC: 33 AN: 223436 AF XY: 0.000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000180

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000110 AC: 159 AN: 1439914 Hom.: 9 Cov.: 85 AF XY: 0.000141 AC XY: 101 AN XY: 716084

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

African (AFR) AF: 0.0000602 AC: 2 AN: 33236

American (AMR) AF: 0.0000230 AC: 1 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.0000786 AC: 3 AN: 38180

South Asian (SAS) AF: 0.000467 AC: 39 AN: 83480

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52208

Middle Eastern (MID) AF: 0.000963 AC: 5 AN: 5192

European-Non Finnish (NFE) AF: 0.0000892 AC: 98 AN: 1098848

Other (OTH) AF: 0.000151 AC: 9 AN: 59488

⚠️ 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 AF: 0.000148 AC: 22 AN: 148376 Hom.: 0 Cov.: 28 AF XY: 0.000207 AC XY: 15 AN XY: 72384

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

African (AFR) AF: 0.0000738 AC: 3 AN: 40636

American (AMR) AF: 0.000137 AC: 2 AN: 14622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.000209 AC: 1 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000240 AC: 16 AN: 66754

Other (OTH) AF: 0.00 AC: 0 AN: 2044

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000777156), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000159 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000193 AC: 1

ExAC AF: 0.000216 AC: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.1
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.16
Sift	Benign	0.050	D
Sift4G	Uncertain	0.015	D
Polyphen		0.49	P
Vest4		0.73
MVP		0.10
MPC		3.4
ClinPred		0.49	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.74
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376073852; hg19: chr8-12042923; COSMIC: COSV58670461; COSMIC: COSV58670461;