rs1613631

Variant names:

• chr12-52382151-T-G
• rs1613631
• NM_033045.4:c.912+286A>C

Variant summary

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

The NM_033045.4(KRT84):​c.912+286A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,066 control chromosomes in the GnomAD database, including 10,141 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 0.32 (10141 hom., cov: 33)
• Consequence: KRT84 NM_033045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 4 publications found

Genes affected

KRT84 (HGNC:6461): (keratin 84) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin is contained primarily in the filiform tongue papilla, among other hair keratins. [provided by RefSeq, Jul 2008]

ENSG00000258253 (HGNC:58283):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT84	NM_033045.4	c.912+286A>C		intron_variant	Intron 4 of 8	ENST00000257951.3	NP_149034.2
KRT84	XM_011538335.3	c.912+286A>C		intron_variant	Intron 5 of 9		XP_011536637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT84	ENST00000257951.3	c.912+286A>C		intron_variant	Intron 4 of 8	1	NM_033045.4	ENSP00000257951.3
ENSG00000258253	ENST00000547174.1	n.146+1546T>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49238 AN: 151948 Hom.: 10131 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.324 AC: 49291 AN: 152066 Hom.: 10141 Cov.: 33 AF XY: 0.324 AC XY: 24086 AN XY: 74346

African (AFR) AF: 0.583 AC: 24164 AN: 41438

American (AMR) AF: 0.330 AC: 5045 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3468

East Asian (EAS) AF: 0.174 AC: 901 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1067 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10586

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14168 AN: 67980

Other (OTH) AF: 0.299 AC: 632 AN: 2114

Alfa AF: 0.298 Hom.: 1381

Bravo AF: 0.341

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.49
PhyloP100		0.12
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: rs1613631; hg19: chr12-52775935;