4-17708963-C-G

Position:

• chr4-17708963-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015688.2(FAM184B):​c.823G>C​(p.Asp275His) variant causes a missense change. The variant allele was found at a frequency of 0.00526 in 1,550,388 control chromosomes in the GnomAD database, including 37 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 0.0032 (6 hom., cov: 29)
  • Exomes 𝑓: 0.0055 (31 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010471642).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM184B	NM_015688.2	c.823G>C	p.Asp275His	missense_variant	2/18	ENST00000265018.4
FAM184B	XM_047450066.1	c.823G>C	p.Asp275His	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184B	ENST00000265018.4	c.823G>C	p.Asp275His	missense_variant	2/18	1	NM_015688.2	P1

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 151916 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.000895

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00574

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00293 AC: 455 AN: 155496 Hom.: 5 AF XY: 0.00294 AC XY: 242 AN XY: 82432

Gnomad AFR exome AF: 0.000632

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00159

Gnomad FIN exome AF: 0.000485

Gnomad NFE exome AF: 0.00538

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00548 AC: 7668 AN: 1398352 Hom.: 31 Cov.: 30 AF XY: 0.00534 AC XY: 3685 AN XY: 689660

Gnomad4 AFR exome AF: 0.000633

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.0000797

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00207

Gnomad4 FIN exome AF: 0.000573

Gnomad4 NFE exome AF: 0.00655

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152036 Hom.: 6 Cov.: 29 AF XY: 0.00293 AC XY: 218 AN XY: 74300

Gnomad4 AFR AF: 0.000892

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.00572

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00416 Hom.: 2

Bravo AF: 0.00360

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00409 AC: 13

ExAC AF: 0.00145 AC: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.010	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.35
ClinPred		0.022	T
GERP RS		5.1
Varity_R		0.67
gMVP		0.33

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: rs61746992; hg19: chr4-17710586; COSMIC: COSV105872416;